ReviewArticle Genetic Epidemiology of Type 2 Diabetes in …downloads.hindawi.com/journals/bmri/2017/3937893.pdf · 2019. 7. 30. · ELMO1 7p14 rs1345365 A/ G Intronic 148;269. (.–.)

Review ArticleGenetic Epidemiology of Type 2 Diabetes in Mexican Mestizos

Eiraliacute Guadalupe Garciacutea-Chapa Evelia Leal-Ugarte Valeria Peralta-LealJorge Duraacuten-Gonzaacutelez and Juan Pablo Meza-Espinoza

Facultad de Medicina e Ingenierıa en Sistemas Computacionales de Matamoros Universidad Autonoma de TamaulipasSendero Nacional Km 3 Col San Jose Matamoros TAMPS 87349 Mexico

Correspondence should be addressed to Juan Pablo Meza-Espinoza sirol1073yahoocommx

Received 14 February 2017 Accepted 18 April 2017 Published 18 May 2017

Academic Editor Joselyn Rojas

Copyright copy 2017 Eiralı Guadalupe Garcıa-Chapa et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

There are currently about 415 million people with diabetes worldwide a figure likely to increase to 642 million by 2040 In 2015Mexico was the second Latin American country and sixth in the world in prevalence of this disorder with nearly 115 million ofpatients Type 2 diabetes (T2D) is the main kind of diabetes and its etiology is complex with environmental and genetic factorsinvolved Indeed polymorphisms in several genes have been associated with this disease worldwide To estimate the geneticepidemiology of T2D inMexicanmestizos a systematic bibliographic search of published articles through PubMed Scopus GoogleScholar andWeb of Science was conducted Just case-control studies of candidate genes about T2D inMexicanmestizo inhabitantswere included Nineteen studies that met the inclusion criteria were found In total 68 polymorphisms of 41 genes were assessed 26of themwere associatedwith T2D risk whichwere located inABCA1 ADRB3 CAPN10 CDC123CAMK1D CDKAL1 CDKN2A2BCRP ELMO1 FTO HHEX IGF2BP2 IRS1 JAZF1 KCNQ1 LOC387761 LTA NXPH1 SIRT1 SLC30A8 TCF7L2 and TNF-120572 genesOverall 21 of the 41 analyzed genes were associated with T2D in Mexican mestizos Such a genetic heterogeneity compares withfindings in other ethnic groups

1 Introduction

Type 2 diabetes (T2D) is a metabolic disorder characterizedby impaired glucose uptake in muscle and fat alteredglucose-induced insulin secretion and increased hepaticglucose production which lead to hyperglycemia It is themost common type of diabetes and generally occurs in adults[1] According to the International Diabetes Federationthere are currently around 415 million people with diabetesworldwide a figure likely to increase to 642 million by2040 [2] This disorder accounts for high morbidity andmortality due to complications like renal failure blindnessamputations cardiovascular disease and cerebrovascularevents [1] In 2015 there were approximately 50 milliondeaths by diabetes worldwide [2] With about 73 millionpatients in 2010 [3] our country was second in Latin Americaand tenth in the world in prevalence of this disorder [4] Fiveyears later the number of diabetic patients was estimated tobe 115 million and our country ranked sixth in the world[2] In 2011 most frequent morbidities by T2D were renal

failure (242) and peripheral circulatory complications(173) and the mortality rate was 70100000 inhabitants(httpfmdiabetesorgwp-contentuploads201411diabe-tes2013INEGIpdf) The complex etiology of T2D includesfactors that influence the risk and evolution of the diseasesuch as ethnicity poor alimentation sedentary lifestyleobesity dyslipidemia and family history [1 5] Regardinggenetics worldwide researches have shown association ofthis disease with numerous allelic variants of nearly 80candidate genes [6] The aim of this study is to carry outa literature review about genetic researches conducted inMexican mestizos for a better understanding of the geneticepidemiology of T2D in our population

2 Methods

A systematic search was done through PubMed ScopusGoogle Scholar and Web of Science for genetic studies con-ducted in Mexican mestizo inhabitants with T2D Key wordsderived from the phrase ldquoGenetic polymorphisms associated

HindawiBioMed Research InternationalVolume 2017 Article ID 3937893 10 pageshttpsdoiorg10115520173937893

2 BioMed Research International

with Diabetes Mellitus type 2 in Mexico Mexican patientsandor Mexican mestizordquo were used Related terms suchas ldquovariantsrdquo ldquoallelesrdquo and ldquoSNP associated with diabetesT2DM or T2Drdquo complemented our search Just case-controlstudies of candidate genes performed in Mexican mestizosresident in the country were included Researches conductedin Mexican native populations were excluded as well asthose done in patients with metabolic syndrome In surveysthat included both patients with metabolic syndrome andpatients with T2D only cases with T2D were registeredAlthough in the selected studies different models of genotypeanalyses were used (recessive dominant or codominant)solely comparisons between allele frequencies were consid-ered in our review In studies without described odds ratio(OR) unadjusted OR were estimated from the reportedallele or genotype frequencies Allele comparisons wereperformed by 2 times 2 contingency tables [Yatesrsquo correction chi-square test (httpvassarstatsnetodds2x2html)] and geno-types were contrasted by chi-square test (httpsihggsfdecgi-binhwhwa2pl) In both comparisons OR were esti-mated using 95 confidence intervals (95 CI) A 119901 le 005defined a significant association

Whenever a polymorphism was analyzed in differentstudies data were combined and unadjusted OR for alleleswere calculated using a 2 times 2 contingency table (Yatesrsquocorrection chi-square test) However studies with suspicionof overlapping of patients were not included in this analysis

3 Results

In total 19 case-control studies on the possible associationof genetic polymorphisms with T2D in Mexican mestizosresident in the country were included [7ndash25] Altogether 68polymorphisms of 41 genes were assessed (Table 1) Of them25 were associated with an increased risk for T2D and theywere located in 20 genes namely ABCA1 ADRB3 CAPN10CDC123CAMK1D CDKN2A2B CRP ELMO1 FTO HHEXIGF2BP2 IRS1 JAZF1 KCNQ1 LOC387761 LTA NXPH1SIRT1 SLC30A8 TCF7L2 and TNF-120572 Among the vari-ants that showed association there were 420 amino acidsubstitutions 1330 intronic sites 610 of promoter regionor 51015840-flanking region or upstream of gene 12 intergenicregions and 26 of 31015840-untranslated or 31015840-flanking regionof gene On the other hand 12 polymorphisms were ana-lyzed by different authors and concordance was observedin most of them except for rs3842570 (CAPN10) [11 1314] rs13266634 (SLC30A4) [8 17] rs7903146 (TCF7L2) [810 12 22] and rs1800629 (TNF-120572) [20 24 25] Eleven ofthese polymorphisms were pooled and analyzed as shownin Table 2 Note that rs4994 (ADRB3) was discarded of thisanalysis (suspicion of overlap of [9 10]) Similarly data byCruz et al [10] for rs7903146 and rs12255372 of TCF7L2were not considered (possible overlapping with the study byMartınez-Gomez et al [12])Thus the 3R allele of rs3842570which was associated with T2D in a small sample did notseemingly confer susceptibility to the disease in contrast theC allele of rs7754840 (CDKAL1) which evidenced no risk inindependent studies showed associationwithT2D Including

this allele a total of 26 polymorphisms and 21 genes wereassociated with T2D in Mexican mestizos

4 Discussion

This review about genetics of T2D in Mexican mestizo sub-jects shows that 26 polymorphisms distributed in 21 genes areassociated with this disease so T2D has a high heterogeneityin our population the same as that in other ethnic groupsTherefore in some individuals alleles of certain genes areinvolved while in others subjects are implicated variants ofdifferent genes A previous conclusion that T2D in Mexicanmestizos is genetically homogeneous was based on an analy-sis of three genetic markers [26] and here appears untenableThough the Mexican mestizo population has a Europeangenetic ancestry near 30 [27] not all the alleles conferringdiabetes risk in Europeans are associated with T2D in ourpopulation [8] These variations could be related to geneticbackground differences in clinical classifications samplesize selection and analysis criteria and environmental factorssuch as obesity lifestyle and diet On the other handresearches in several ethnic groups have shown associationof T2D with genes not yet analyzed in Mexican population[5 6 28ndash32] It would be important to carry out the analysisof such genes to determine whether these variants are alsoassociated with T2D in Mexican patients and increase theknowledge about the genetic epidemiology of this disorderin our country

Regarding Mexican studies an increased risk wasdetected when analysis was performed adjusting covariatesFor instance Cruz et al observed an additive effect in theT2Drisk when they considered variables such as age educationsex body mass index and ancestry [10] Gamboa-Melendezet al reported association with T2D for the polymorphismsrs7923837 (HHEX) rs4402960 (IGF2BP2) and rs2237892(KCNQ1) only when ancestry was adjusted [8] For thepolymorphisms rs864745 (JAZF1) and rs757705 (NXPH1)the analysis stratified by ancestry did not show significantdifferences whereas an association was observed in thecomparison without such an adjustment In addition theyfound association for rs7903146 (TCF7L2) and rs7754840(CDKAL1) just in early-onset T2D [OR = 139 (104ndash185) 119901 =0024] and in nonobese T2D patients [OR = 125 (106ndash149)119901 = 0009] respectively Another study found a lower ORwhen the analysis was adjusted by sex body mass index andfamily history of T2D for three polymorphisms of IRS1 in adominant model [19]

The reported association of rs3842570 (CAPN10) [14]rs909253 (LTA) [20] and rs1800629 (TNF-120572) [24] with T2Dshould be interpreted with caution given the small samplesizes and poor statistical powerWith respect to the rs1345365polymorphism (ELMO1) the authors reported a protectoreffect for the A allele [OR = 065 (055ndash078) p lt 0001] [16]But in our analysis we took as reference the A allele as it isthe most common thus the G allele showed association withT2D [OR = 137 (102 to 184) 119901 = 0035]

Since T2D is a complex disorder and several genes areimplicated in its etiology and evolution the identification

BioMed Research International 3

Table1Analyzedgenesinstu

dies

abou

ttype2

diabetes

cond

uctedin

Mexican

mestizos

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

ABCA

19q31

rs9282541

CT

RC

244202

250

(148ndash

424

)000

1[7]

rs2000

069

CT

Intro

nic

244202

108(082ndash14

2)c

058

[7]

rs2230806

GA

RK

244202

117(089ndash

155)

c027

[7]

rs2487037

CT

Intro

nic

244202

106(079ndash

143)

c071

[7]

rs3818689

GC

Intro

nic

244202

094

(052

ndash168)

c082

[7]

ADAM

TS9

3p14

rs46

07103

CT

Intro

nic

1027990

105(091ndash12

0)d

0521

[8]

ADRB

110q25

rs1801253

CG

RG

501552

079

(061ndash10

2)c

007

[9]

ADRB

38p11

rs4994

CT

WR

519547

169(137ndash

209

)c000

01[10]

rs4994

CT

WR

501552

134(110

ndash164)

c000

4[9]

ARHGE

F11

1q21

rs945508

GA

RH

868504

091

(076

ndash109)

e0319

[8]

CAPN

102q37

rs3792267

GA

Intro

nic

132112

097

(066ndash

142)

c086

[11]

rs3792267

GA

Intro

nic

719746

111(095ndash129)

cf020

[12]

rs3792267

GA

Intro

nic

211152

091

(066ndash

126)

056

[13]

rs3842570

2R3R

Intro

nic

132112

097

(068ndash14

0)c

089

[11]

rs3842570

2R3R

Intro

nic

4364

181(10

3ndash318)c

003

8[14

]rs3842570

2R3R

Intro

nic

211152

075

(055ndash10

2)006

[13]

rs5030952

CT

Intro

nic

132113

085

(056ndash

129)

c045

[11]

rs5030952

CT

Intro

nic

211152

135(089ndash

206)

016

[13]

rs2975760

TC

Intro

nic

134113

272

(116

ndash635)

0017

[11]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

CAPN

102q37

rs7607759

AG

TA

127110

227

(098ndash525)c

0051

[11]

CDC123CAM

K1D

10p13

rs12779790

AG

Intergenic

1027990

124(105ndash14

7)d

0013

[8]

CDKA

L16p

22

rs10946398

AC

Intro

nic

519547

109(091ndash13

2)c

0337

[10]

rs9465871

CT

Intro

nic

519547

104(085ndash12

6)c

0718

[10]

rs7754840

CG

Intro

nic

519547

108(089ndash

129)

c0438

[10]

rs7754840

CG

Intro

nic

1027990

113(098ndash13

0)dg

0081

[8]

CDKN

2A2B

9p21

rs10811661

CT

Upstre

am1027990

142(115

ndash175)

d000

1[8]

CRP

1q23

rs1130864

CT

31015840-U

TR166130

159(115

ndash222)

chi

000

5[15]

rs1205

GA

31015840-U

TR166130

082

(059ndash

114)

chi

024

[15]

rs2794521

AG

51015840-flanking

166130

197(115

ndash338)

chi

0012

[15]

rs3093062

GA

Prom

oter

166130

349

(098ndash

124)c

hi

0039

[15]

ELMO1

7p14

rs1345365

AG

Intro

nic

148269

137(102ndash

184)

chi

0035

[16]

ENPP

16q

23rs1044

498

AC

KQ

519547

094

(076

ndash116

)c0577

[10]

EXT2

11p11

rs3740

878

AG

Intro

nic

455234

083

(065ndash10

5)0054

[17]

FTO

16q12

rs8050136

AC

Intro

nic

868504

090

(074

ndash109)

e0278

[8]

rs993960

9AT

Intro

nic

519547

125(102ndash

154)

c0027

[10]

HHEX

10q23

rs5015480

CT

Upstre

am519547

096

(080ndash

114)

c0631

[10]

rs111

1875

CT

31015840-flanking

1027990

101(089ndash116

)d0859

[8]

rs111

1875

CT

31015840-flanking

455234

112(088ndash14

4)027

[17]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

HHEX

10q23

rs7923837

AG

31015840-flanking

868504

121(10

2ndash14

4)k

002

5[8]

HMOX1

22q12

rs2071749

AG

Prom

oter

614956

098

(084ndash

114)

c076

[18]

IGF2BP

23q27

rs44

02960

GT

Intro

nic

868504

124(101ndash15

3)j

004

2[8]

IRS1

2q36

rs1801278

GA

GR

719746

204

(141ndash296

)cf

lt000

1[12]

rs1801278

GA

GR

44444

4322

(199ndash

520

)000

1[19

]rs1801276

CG

PA

44444

4098

(072ndash13

2)083

[19]

rs3731594

GA

ND

44444

4083

(042ndash16

6)047

[19]

rs1801108

GC

RP

44444

410

7(085ndash13

4)040

[19]

JAZF

17p15

rs864745

TC

Intro

nic

868504

124(104ndash

147)

k0015

[8]

KCNJ11

11p15

rs5215

CT

VI

519547

103(087ndash12

3)c

0729

[10]

rs5210

AG

31015840-U

TR519547

103(086ndash

123)

c0764

[10]

rs5219

CT

EK

1027990

110(096ndash

126)

d0154

[8]

KCNQ1

11p15

rs2237892

CT

Intro

nic

868504

136(113

ndash164)

k000

1[8]

LEPR

1p31

rs1137100

AG

KR

519547

100(084ndash

121)

c092

[10]

LOC3

87761

11p12

rs7480010

AG

Intro

nic

455234

143(105ndash19

4)000

6[17]

LTA

6p21

rs909253

AG

Intro

nic

5148

198(102ndash

38)

c004

1[20]

MGE

A510q24

MGEA

5-14

AT

Intro

nic

271244

160(052

ndash486)

040

4[21]

NOTC

H2

1p11

rs10923931

GT

Intro

nic

1027990

104(082ndash13

2)d

0731

[8]

NQO1

16q22

rs1800566

CT

PS

623993

098

(085ndash113)

c076

[18]

NRF

22q31

rs2364723

CG

Intro

nic

625992

091

(079ndash

105)

c018

[18]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

NRF

22q31

rs6721961

CA

Prom

oter

623989

089

(074

ndash106)

c018

[8]

NXP

H1

7p22

rs757705

AG

Intro

nic

868504

125(105ndash14

8)k

001

[8]

PPAR

G3p25

rs1801282

CG

PA

719746

100(081ndash12

4)cf

100

[12]

rs1801282

CG

PA

1027990

110(090ndash

134)

d0342

[8]

rs17793693

AC

Intro

nic

519547

109(091ndash13

1)c

0329

[10]

RALG

PS2

1q25

rs2773080

AG

Intro

nic

868504

090

(074

ndash110

)e0315

[8]

RORA

15q22

rs7164773

CT

Intro

nic

868504

108(091ndash12

8)e

0357

[8]

SIRT

110q21

rs3758391

CT

Upstre

am519547

129(108ndash

154)

c000

4[10]

SLC3

0A4

8q24

rs13266634

CT

RW

455234

101(076ndash133

)092

[17]

rs13266634

CT

RW

1027990

122(105ndash14

1)d

000

9[8]

TCF7L2

10q25

rs7903146

CT

Intro

nic

868504

104(084ndash

128)

el0735

[8]

rs7903146

CT

Intro

nic

200200

184(105ndash320

)cm

004

[12]

rs7903146

CT

Intro

nic

519547

148(118

ndash186)

c000

07[10]

rs7903146

CT

Intro

nic

283271

125(092ndash17

0)016

[22]

rs12255372

GT

Intro

nic

200200

183(121ndash276)c

m000

6[12]

rs12255372

GT

Intro

nic

281268

178(111ndash2

88)

0017

[22]

rs12255372

GT

Intro

nic

519547

137(106ndash

176)

c0014

[10]

DG10S478

STRCA

CAIntro

nic

282274

162(102ndash

257)

004

1[22]

TLR2

4q32

rs5743708

GA

RQ

321538

041

(004ndash

37)

040

[23]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

TLR4

9q33

rs4986790

AG

DG

321538

139(042ndash456)

058

[23]

rs4986791

CT

TI

321538

101(032ndash318

)098

[23]

TNF-120572

6p21

rs1800

629

-308GA

Upstre

am5148

076

(031

ndash185)

cn055

[20]

rs1800

629

-308GA

Upstre

am9587

466

(173ndash125)c

000

1[24]

rs1800

629

-308GA

Upstre

am25964

512

5(083ndash18

7)029

[25]

rs361525

-238GA

Upstre

am25964

515

7(107ndash

229

)0018

[25]

TSPA

N8LG

R512q14ndash

q21

rs7961581

CT

Intergenic

868504

093

(073ndash117)

e0516

[8]

TXNIP

1q21

rs7211

CT

31015840UTR

623969

097

(082ndash114)

067

[18]

UBQ

LNL

11p15

rs979752

CT

Upstre

am868504

104(084ndash

130)

e070

[8]

Chromchrom

osom

eRisk

alleles

arem

arkedin

bold119899

a 119899b Samplefor

casesa

ndcontrols

respectiv

elycCon

ventionalO

R(unadjusted)

was

assessed

byus

from

alleleor

geno

type

frequ

encies

repo

rteddLargest119899

was

registe

red

e Testw

ithou

tancestrycorrectio

nwas

consideredfCom

bineddatasetswerer

egisteredgRisk

was

onlyob

served

inno

nobese

T2Dpatients(OR=12

5119901=0009)

h OnlyGenotypes

ofT2

Dpatients

andhealthycontrolswereu

sedin

oura

nalysisiAssessm

entd

erived

from

thes

umof

T2Dpatients(ob

esea

ndno

nobese)

j Thea

utho

rsrepo

rted

aprotectore

ffectforthe

Aallele(

OR=065plt0001)but

inou

restim

ationwetoo

kas

referencethe

Aallelesin

ceitisthem

ostcom

mon

kSign

ificant

analysiswith

ancestr

ycorrectio

nwas

taken

l Associatio

nwas

onlyfoun

din

early

-onsetT2

D(O

R=13

9119901=0024)

mJustthe

popu

lationof

Guerrerowas

recorded

duetopo

ssibleoverlap

ping

ofthep

atientsfrom

theM

exicoCity

with

[10]nTh

eGallelew

asassessed

asris

kby

thea

utho

rsbut

inou

ranalysis

wetoo

ktheA

allelethes

ame

asthatin

previous

studies


Table2Analysis

ofSN

Psstu

died

bytwoor

moreg

roup

sinMexican

mestizos

Gene

dbSN

Ploc

Cases

(allele)

Con

trols

(allele)

Risk

allelefre

quency

()

OR(95

CI)

119901lowastvalue

Reference

Cases

Con

trols

CAPN

10rs3792267

1086

928

295

287

106(087ndash12

9)056

[11ndash13]

CAPN

10rs3842570

772

656

617

625

096

(078ndash12

0)074

[111314]

CAPN

10rs5030952

686

530

190

183

104(078ndash14

0)078

[1113]

CDKA

L1rs7754840

3092

3074

314

291

112(100ndash

125)

004

4[810]

HHEX

rs11118

752974

2448

628

617

105(094ndash

117)

043

[817]

IRS1

rs1801278

2326

2380

66

28

245

(183ndash328

)lt000

01[1219]

PPAR

Grs1801282

3492

3472

873

867

105(091ndash12

1)051

[812]

SLC3

0A4

rs13266634

2964

2448

763

730

119(105ndash13

5)000

5[817]

TCF7L2

rs7903146

3740

3042

178

141

132(116

ndash150)

lt000

01[81222]

TCF7L2

rs12255372

2476

2586

183

116

140(119

ndash165)

lt000

01[1222]

TNF-120572

rs1800

629

810

1560

115

62

196(145ndash264

)lt000

01[202425]

lowastYatesrsquocorrectio

nchi-squ

aretest


of risk alleles could be useful because if the involved genesand their function are known it is more probable to achieveprevention treatment prognosis andor cure of the diseaseComplications could also be prevented or treated better [2933] However published studies demonstrate that geneticscreening for the prediction of T2D in high risk subjects iscurrently of little value in clinical practice Actually geneticrisks are difficult to calculate because several alleles couldcontribute to an additive effect to T2D susceptibility [34]not to mention the diverse environmental factors involvedAlthough some of these genes are implicated in the glucoseand fat metabolism 120573-cell function and sensitivity andsecretion of insulin [29 35] how some of their variantsincrease the T2D risk remains to be elucidated [29] Anywayit is fundamental to analyze the genetic epidemiology ofthis disease in each population because of the underlyingdifferences in genetic background and lifestyle among ethnicgroups So it is possible that polymorphisms associatedwith T2D in some races do not show association in othersGenome-wide association studies will ultimately precise thegenetic landscape

Conflicts of Interest

The authors declare no conflicts of interest concerning thepublication of this paper

Authorsrsquo Contributions

Eiralı Guadalupe Garcıa-Chapa and Juan Pablo Meza-Espinoza contributed equally to this work All the authorsparticipated in drafting and review of this paper

Acknowledgments

The authors thank Dr Horacio Rivera for his support andcritical review of the manuscript

References

[1] American Diabetes Association ldquoStandards of medical care indiabetesmdash2013rdquo Diabetes Care vol 36 supplement 1 pp S11-S66 2013

[2] International Diabetes Federation ldquoIDF diabetes atlasrdquo inInternational Diabetes Federation pp 1ndash144 Brussels Belgium7th edition 2015 httpwwwdiabetesatlasorg

[3] S Villalpando V de la Cruz R Rojas et al ldquoPrevalenceand distribution of type 2 diabetes mellitus in Mexican adultpopulation A probabilistic surveyrdquo Salud Publica de Mexicovol 52 supplement 1 pp s19-s26 2010

[4] J E Shaw R A Sicree and P Z Zimmet ldquoGlobal estimates ofthe prevalence of diabetes for 2010 and 2030rdquoDiabetes Researchand Clinical Practice vol 87 no 1 pp 4ndash14 2010

[5] V Lyssenko A Jonsson P Almgren et al ldquoClinical risk factorsDNA variants and the development of type 2 diabetesrdquo NewEngland Journal of Medicine vol 359 no 21 pp 2220ndash22322008

[6] A Stancakova and M Laakso ldquoGenetics of type 2 diabetesrdquoEndocrine Development vol 31 pp 203ndash220 2016

[7] M T Villarreal-Molina M T Flores-Dorantes O Arellano-Campos et al ldquoAssociation of the ATP-binding cassette trans-porter A1 R230C variant with early-onset type 2 diabetes in aMexican populationrdquoDiabetes vol 57 no 2 pp 509ndash513 2008

[8] M A Gamboa-Melendez A Huerta-Chagoya H Moreno-Macıas et al ldquoContribution of common genetic variation tothe risk of type 2 diabetes in the Mexican Mestizo populationrdquoDiabetes vol 61 no 12 pp 3314ndash3321 2012

[9] A I Burguete-Garcıa G A Martınez-Nava A Valladares-Salgado et al ldquoAssociation of 1205731 and 1205733 adrenergic receptorsgene polymorphisms with insulin resistance and high lipidprofiles related to type 2 diabetes and metabolic syndromerdquoNutricion Hospitalaria vol 29 no 6 pp 1327ndash1334 2014

[10] M Cruz A Valladares-Salgado J Garcıa-Mena et al ldquoCandi-date gene association study conditioning on individual ancestryin patients with type 2 diabetes and metabolic syndrome fromMexico Cityrdquo Diabetes Metabolism Research and Reviews vol26 no 4 pp 261ndash270 2010

[11] L Del Bosque-Plata C A Aguilar-Salinas M T Tusie-Lunaet al ldquoAssociation of the calpain-10 gene with type 2 diabetesmellitus in a Mexican populationrdquo Molecular Genetics andMetabolism vol 81 no 2 pp 122ndash126 2004

[12] L E Martınez-Gomez M Cruz G A Martınez-Nava et al ldquoAreplication study of the IRS1 CAPN10 TCF7L2 and PPARGgene polymorphisms associated with type 2 diabetes in twodifferent populations ofMexicordquoAnnals ofHumanGenetics vol75 no 5 pp 612ndash620 2011

[13] V J Picos-Cardenas E Sainz-Gonzalez A Miliar-Garcıa et alldquoCalpain-10 gene polymorphisms and risk of type 2 diabetesmellitus inMexicanmestizosrdquoGenetics andMolecular Researchvol 14 no 1 pp 2205ndash2215 2015

[14] Y Loya-Mendez G Reyes Leal A SanchezGonzalez V PortilloReyes D Reyes Ruvalcaba and G Bojorquez Rangel ldquoSNP-19genotypic variants of CAPN10 gene and its relation to diabetesmellitus type 2 in a population of Ciudad Juarezrdquo NutricionHospitalaria vol 31 no 2 pp 744ndash750 2015

[15] A Martınez-Calleja I Quiroz-Vargas I Parra-Rojas et alldquoHaplotypes in the CRP gene associated with increased BMIand levels of CRP in subjects with type 2 diabetes or obesityfrom Southwestern Mexicordquo Experimental Diabetes Researchvol 2012 7 pages 2012 Article ID 982683

[16] S A Ramirez-Garcia C Charles-Nino M Mazariegos-Rubıet al ldquoAssociation of the ELMO1 gene (Snp rs1345365) withdevelopment of type 2 diabetes mellitus in the mexican mestizopopulationrdquo Investigacion Clinica (Venezuela) vol 56 no 4 pp341ndash355 2015

[17] R Gutierrez-Vidal A Rodrıguez-Trejo S Canizales-Quinteroset al ldquoLOC387761 polymorphism is associated with type2 diabetes in the Mexican populationrdquo Genetic Testing andMolecular Biomarkers vol 15 no 1-2 pp 79ndash83 2011

[18] A S Jimenez-Osorio S Gonzalez-Reyes W R Garcıa-Ninoet al ldquoAssociation of nuclear factor-erythroid 2-related factor2 thioredoxin interacting protein and heme oxygenase-1 genepolymorphisms with diabetes and obesity in mexican patientsrdquoOxidative Medicine and Cellular Longevity vol 2016 Article ID7367641 8 pages 2016

[19] A I Burguete-Garcia M Cruz-Lopez V Madrid-Marina etal ldquoAssociation of Gly972Arg polymorphism of IRS1 gene withtype 2 diabetes mellitus in lean participants of a national healthsurvey in Mexico a candidate gene studyrdquoMetabolism Clinicaland Experimental vol 59 no 1 pp 38ndash45 2010


[20] G Garcıa-Elorriaga M Mendoza-Aguilar G del Rey-PinedaandCGonzalez-Bonilla ldquoGenetic polymorphisms of the tumornecrosis factor and lymphotoxin alpha in type 2 diabetesrdquoRevista Medica del Instituto Mexicano del Seguro Social vol 51no 1 pp 42ndash49 2013

[21] E A Cameron V L Martinez-Marignac A Chan et alldquoMGEA5-14 polymorphism and type 2 diabetes inMexico CityrdquoAmerican Journal of Human Biology vol 19 no 4 pp 593ndash5962007

[22] E J Parra L Cameron L Simmonds et al ldquoAssociation ofTCF7L2 polymorphisms with type 2 diabetes in Mexico CityrdquoClinical Genetics vol 71 no 4 pp 359ndash366 2007

[23] C Maldonado-Bernal O A Trejo-de la M E Sanchez-Contreras N Wacher-Rodarte J Torres and M Cruz ldquoLowfrequency of Toll-like receptors 2 and 4 gene polymorphismsin Mexican patients and their association with type 2 diabetesrdquoInternational Journal of Immunogenetics vol 38 no 6 pp 519ndash523 2011

[24] E Perez-Luque J M Malacara M E Garay-Sevilla and ME Fajardo ldquoAssociation of the TNF-120572 -308GA polymorphismwith family history of type 2 diabetes mellitus in a Mexicanpopulationrdquo Clinical Biochemistry vol 45 no 1-2 pp 12ndash152012

[25] J M Guzman-Flores J F Munoz-Valle J Sanchez-Coronaet al ldquoTumor necrosis factor-alpha gene promoter minus308GAand minus238GA polymorphisms in Mexican patients with type 2diabetesmellitusrdquoDiseaseMarkers vol 30 no 1 pp 19ndash24 2011

[26] R M Cerda-Flores R A Rivera-Prieto B Pereyra-Alferez etal ldquoGenetic structure of MexicanMestizos with type 2 diabetesmellitus based on three STR locirdquoGene vol 525 no 1 pp 41ndash462013

[27] V L Martinez-Marignac A Valladares E Cameron et alldquoAdmixture in Mexico City Implications for admixture map-ping of Type 2 diabetes genetic risk factorsrdquo Human Geneticsvol 120 no 6 pp 807ndash819 2007

[28] Q Ayub L Moutsianas Y Chen et al ldquoRevisiting the thriftygene hypothesis via 65 loci associated with susceptibility to type2 diabetesrdquo American Journal of Human Genetics vol 94 no 2pp 176ndash185 2014

[29] S H Kwak and K S Park ldquoGenetics of type 2 diabetes andpotential clinical implicationsrdquo Archives of Pharmacal Researchvol 36 no 2 pp 167ndash177 2013

[30] E Ahlqvist T S Ahluwalia and L Groop ldquoGenetics of type 2diabetesrdquo Clinical Chemistry vol 57 no 2 pp 241ndash254 2011

[31] N D Palmer C W McDonough P J Hicks et al ldquoA genome-wide association search for type 2 diabetes genes in africanamericansrdquo PLoS ONE vol 7 no 1 Article ID e29202 2012

[32] C S Janipalli M V K Kumar D G Vinay et al ldquoAnalysis of32 common susceptibility genetic variants and their combinedeffect in predicting risk of Type 2 diabetes and related traits inIndiansrdquo Diabetic Medicine vol 29 no 1 pp 121ndash127 2012

[33] S K Das ldquoGenetic epidemiology of adult onset type 2 diabetesin Asian Indian population past present and futurerdquo Interna-tional Journal of Human Genetics vol 6 no 1 pp 1ndash13 2006

[34] V Lyssenko and M Laakso ldquoGenetic screening for the risk oftype 2 diabetes worthless or valuablerdquo Diabetes Care vol 36supplement 2 pp S120-S126 2013

[35] A M Simonis-Bik G Nijpels T W Van Haeften et al ldquoGenevariants in the novel type 2 diabetes loci CDC123CAMK1DTHADA ADAMTS9 BCL11A and MTNR1B affect differentaspects of pancreatic 120573-cell functionrdquo Diabetes vol 59 no 1pp 293ndash301 2010

Submit your manuscripts athttpswwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


with Diabetes Mellitus type 2 in Mexico Mexican patientsandor Mexican mestizordquo were used Related terms suchas ldquovariantsrdquo ldquoallelesrdquo and ldquoSNP associated with diabetesT2DM or T2Drdquo complemented our search Just case-controlstudies of candidate genes performed in Mexican mestizosresident in the country were included Researches conductedin Mexican native populations were excluded as well asthose done in patients with metabolic syndrome In surveysthat included both patients with metabolic syndrome andpatients with T2D only cases with T2D were registeredAlthough in the selected studies different models of genotypeanalyses were used (recessive dominant or codominant)solely comparisons between allele frequencies were consid-ered in our review In studies without described odds ratio(OR) unadjusted OR were estimated from the reportedallele or genotype frequencies Allele comparisons wereperformed by 2 times 2 contingency tables [Yatesrsquo correction chi-square test (httpvassarstatsnetodds2x2html)] and geno-types were contrasted by chi-square test (httpsihggsfdecgi-binhwhwa2pl) In both comparisons OR were esti-mated using 95 confidence intervals (95 CI) A 119901 le 005defined a significant association

Whenever a polymorphism was analyzed in differentstudies data were combined and unadjusted OR for alleleswere calculated using a 2 times 2 contingency table (Yatesrsquocorrection chi-square test) However studies with suspicionof overlapping of patients were not included in this analysis

3 Results

In total 19 case-control studies on the possible associationof genetic polymorphisms with T2D in Mexican mestizosresident in the country were included [7ndash25] Altogether 68polymorphisms of 41 genes were assessed (Table 1) Of them25 were associated with an increased risk for T2D and theywere located in 20 genes namely ABCA1 ADRB3 CAPN10CDC123CAMK1D CDKN2A2B CRP ELMO1 FTO HHEXIGF2BP2 IRS1 JAZF1 KCNQ1 LOC387761 LTA NXPH1SIRT1 SLC30A8 TCF7L2 and TNF-120572 Among the vari-ants that showed association there were 420 amino acidsubstitutions 1330 intronic sites 610 of promoter regionor 51015840-flanking region or upstream of gene 12 intergenicregions and 26 of 31015840-untranslated or 31015840-flanking regionof gene On the other hand 12 polymorphisms were ana-lyzed by different authors and concordance was observedin most of them except for rs3842570 (CAPN10) [11 1314] rs13266634 (SLC30A4) [8 17] rs7903146 (TCF7L2) [810 12 22] and rs1800629 (TNF-120572) [20 24 25] Eleven ofthese polymorphisms were pooled and analyzed as shownin Table 2 Note that rs4994 (ADRB3) was discarded of thisanalysis (suspicion of overlap of [9 10]) Similarly data byCruz et al [10] for rs7903146 and rs12255372 of TCF7L2were not considered (possible overlapping with the study byMartınez-Gomez et al [12])Thus the 3R allele of rs3842570which was associated with T2D in a small sample did notseemingly confer susceptibility to the disease in contrast theC allele of rs7754840 (CDKAL1) which evidenced no risk inindependent studies showed associationwithT2D Including

this allele a total of 26 polymorphisms and 21 genes wereassociated with T2D in Mexican mestizos

4 Discussion

This review about genetics of T2D in Mexican mestizo sub-jects shows that 26 polymorphisms distributed in 21 genes areassociated with this disease so T2D has a high heterogeneityin our population the same as that in other ethnic groupsTherefore in some individuals alleles of certain genes areinvolved while in others subjects are implicated variants ofdifferent genes A previous conclusion that T2D in Mexicanmestizos is genetically homogeneous was based on an analy-sis of three genetic markers [26] and here appears untenableThough the Mexican mestizo population has a Europeangenetic ancestry near 30 [27] not all the alleles conferringdiabetes risk in Europeans are associated with T2D in ourpopulation [8] These variations could be related to geneticbackground differences in clinical classifications samplesize selection and analysis criteria and environmental factorssuch as obesity lifestyle and diet On the other handresearches in several ethnic groups have shown associationof T2D with genes not yet analyzed in Mexican population[5 6 28ndash32] It would be important to carry out the analysisof such genes to determine whether these variants are alsoassociated with T2D in Mexican patients and increase theknowledge about the genetic epidemiology of this disorderin our country

Regarding Mexican studies an increased risk wasdetected when analysis was performed adjusting covariatesFor instance Cruz et al observed an additive effect in theT2Drisk when they considered variables such as age educationsex body mass index and ancestry [10] Gamboa-Melendezet al reported association with T2D for the polymorphismsrs7923837 (HHEX) rs4402960 (IGF2BP2) and rs2237892(KCNQ1) only when ancestry was adjusted [8] For thepolymorphisms rs864745 (JAZF1) and rs757705 (NXPH1)the analysis stratified by ancestry did not show significantdifferences whereas an association was observed in thecomparison without such an adjustment In addition theyfound association for rs7903146 (TCF7L2) and rs7754840(CDKAL1) just in early-onset T2D [OR = 139 (104ndash185) 119901 =0024] and in nonobese T2D patients [OR = 125 (106ndash149)119901 = 0009] respectively Another study found a lower ORwhen the analysis was adjusted by sex body mass index andfamily history of T2D for three polymorphisms of IRS1 in adominant model [19]

The reported association of rs3842570 (CAPN10) [14]rs909253 (LTA) [20] and rs1800629 (TNF-120572) [24] with T2Dshould be interpreted with caution given the small samplesizes and poor statistical powerWith respect to the rs1345365polymorphism (ELMO1) the authors reported a protectoreffect for the A allele [OR = 065 (055ndash078) p lt 0001] [16]But in our analysis we took as reference the A allele as it isthe most common thus the G allele showed association withT2D [OR = 137 (102 to 184) 119901 = 0035]

Since T2D is a complex disorder and several genes areimplicated in its etiology and evolution the identification



dies

abou

ttype2

diabetes

cond

uctedin

Mexican

mestizos

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

ABCA

19q31

rs9282541

CT

RC

244202

250

(148ndash

424

)000

1[7]

rs2000

069

CT

Intro

nic

244202

108(082ndash14

2)c

058

[7]

rs2230806

GA

RK

244202

117(089ndash

155)

c027

[7]

rs2487037

CT

Intro

nic

244202

106(079ndash

143)

c071

[7]

rs3818689

GC

Intro

nic

244202

094

(052

ndash168)

c082

[7]

ADAM

TS9

3p14

rs46

07103

CT

Intro

nic

1027990

105(091ndash12

0)d

0521

[8]

ADRB

110q25

rs1801253

CG

RG

501552

079

(061ndash10

2)c

007

[9]

ADRB

38p11

rs4994

CT

WR

519547

169(137ndash

209

)c000

01[10]

rs4994

CT

WR

501552

134(110

ndash164)

c000

4[9]

ARHGE

F11

1q21

rs945508

GA

RH

868504

091

(076

ndash109)

e0319

[8]

CAPN

102q37

rs3792267

GA

Intro

nic

132112

097

(066ndash

142)

c086

[11]

rs3792267

GA

Intro

nic

719746

111(095ndash129)

cf020

[12]

rs3792267

GA

Intro

nic

211152

091

(066ndash

126)

056

[13]

rs3842570

2R3R

Intro

nic

132112

097

(068ndash14

0)c

089

[11]

rs3842570

2R3R

Intro

nic

4364

181(10

3ndash318)c

003

8[14

]rs3842570

2R3R

Intro

nic

211152

075

(055ndash10

2)006

[13]

rs5030952

CT

Intro

nic

132113

085

(056ndash

129)

c045

[11]

rs5030952

CT

Intro

nic

211152

135(089ndash

206)

016

[13]

rs2975760

TC

Intro

nic

134113

272

(116

ndash635)

0017

[11]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

CAPN

102q37

rs7607759

AG

TA

127110

227

(098ndash525)c

0051

[11]

CDC123CAM

K1D

10p13

rs12779790

AG

Intergenic

1027990

124(105ndash14

7)d

0013

[8]

CDKA

L16p

22

rs10946398

AC

Intro

nic

519547

109(091ndash13

2)c

0337

[10]

rs9465871

CT

Intro

nic

519547

104(085ndash12

6)c

0718

[10]

rs7754840

CG

Intro

nic

519547

108(089ndash

129)

c0438

[10]

rs7754840

CG

Intro

nic

1027990

113(098ndash13

0)dg

0081

[8]

CDKN

2A2B

9p21

rs10811661

CT

Upstre

am1027990

142(115

ndash175)

d000

1[8]

CRP

1q23

rs1130864

CT

31015840-U

TR166130

159(115

ndash222)

chi

000

5[15]

rs1205

GA

31015840-U

TR166130

082

(059ndash

114)

chi

024

[15]

rs2794521

AG

51015840-flanking

166130

197(115

ndash338)

chi

0012

[15]

rs3093062

GA

Prom

oter

166130

349

(098ndash

124)c

hi

0039

[15]

ELMO1

7p14

rs1345365

AG

Intro

nic

148269

137(102ndash

184)

chi

0035

[16]

ENPP

16q

23rs1044

498

AC

KQ

519547

094

(076

ndash116

)c0577

[10]

EXT2

11p11

rs3740

878

AG

Intro

nic

455234

083

(065ndash10

5)0054

[17]

FTO

16q12

rs8050136

AC

Intro

nic

868504

090

(074

ndash109)

e0278

[8]

rs993960

9AT

Intro

nic

519547

125(102ndash

154)

c0027

[10]

HHEX

10q23

rs5015480

CT

Upstre

am519547

096

(080ndash

114)

c0631

[10]

rs111

1875

CT

31015840-flanking

1027990

101(089ndash116

)d0859

[8]

rs111

1875

CT

31015840-flanking

455234

112(088ndash14

4)027

[17]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

HHEX

10q23

rs7923837

AG

31015840-flanking

868504

121(10

2ndash14

4)k

002

5[8]

HMOX1

22q12

rs2071749

AG

Prom

oter

614956

098

(084ndash

114)

c076

[18]

IGF2BP

23q27

rs44

02960

GT

Intro

nic

868504

124(101ndash15

3)j

004

2[8]

IRS1

2q36

rs1801278

GA

GR

719746

204

(141ndash296

)cf

lt000

1[12]

rs1801278

GA

GR

44444

4322

(199ndash

520

)000

1[19

]rs1801276

CG

PA

44444

4098

(072ndash13

2)083

[19]

rs3731594

GA

ND

44444

4083

(042ndash16

6)047

[19]

rs1801108

GC

RP

44444

410

7(085ndash13

4)040

[19]

JAZF

17p15

rs864745

TC

Intro

nic

868504

124(104ndash

147)

k0015

[8]

KCNJ11

11p15

rs5215

CT

VI

519547

103(087ndash12

3)c

0729

[10]

rs5210

AG

31015840-U

TR519547

103(086ndash

123)

c0764

[10]

rs5219

CT

EK

1027990

110(096ndash

126)

d0154

[8]

KCNQ1

11p15

rs2237892

CT

Intro

nic

868504

136(113

ndash164)

k000

1[8]

LEPR

1p31

rs1137100

AG

KR

519547

100(084ndash

121)

c092

[10]

LOC3

87761

11p12

rs7480010

AG

Intro

nic

455234

143(105ndash19

4)000

6[17]

LTA

6p21

rs909253

AG

Intro

nic

5148

198(102ndash

38)

c004

1[20]

MGE

A510q24

MGEA

5-14

AT

Intro

nic

271244

160(052

ndash486)

040

4[21]

NOTC

H2

1p11

rs10923931

GT

Intro

nic

1027990

104(082ndash13

2)d

0731

[8]

NQO1

16q22

rs1800566

CT

PS

623993

098

(085ndash113)

c076

[18]

NRF

22q31

rs2364723

CG

Intro

nic

625992

091

(079ndash

105)

c018

[18]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

NRF

22q31

rs6721961

CA

Prom

oter

623989

089

(074

ndash106)

c018

[8]

NXP

H1

7p22

rs757705

AG

Intro

nic

868504

125(105ndash14

8)k

001

[8]

PPAR

G3p25

rs1801282

CG

PA

719746

100(081ndash12

4)cf

100

[12]

rs1801282

CG

PA

1027990

110(090ndash

134)

d0342

[8]

rs17793693

AC

Intro

nic

519547

109(091ndash13

1)c

0329

[10]

RALG

PS2

1q25

rs2773080

AG

Intro

nic

868504

090

(074

ndash110

)e0315

[8]

RORA

15q22

rs7164773

CT

Intro

nic

868504

108(091ndash12

8)e

0357

[8]

SIRT

110q21

rs3758391

CT

Upstre

am519547

129(108ndash

154)

c000

4[10]

SLC3

0A4

8q24

rs13266634

CT

RW

455234

101(076ndash133

)092

[17]

rs13266634

CT

RW

1027990

122(105ndash14

1)d

000

9[8]

TCF7L2

10q25

rs7903146

CT

Intro

nic

868504

104(084ndash

128)

el0735

[8]

rs7903146

CT

Intro

nic

200200

184(105ndash320

)cm

004

[12]

rs7903146

CT

Intro

nic

519547

148(118

ndash186)

c000

07[10]

rs7903146

CT

Intro

nic

283271

125(092ndash17

0)016

[22]

rs12255372

GT

Intro

nic

200200

183(121ndash276)c

m000

6[12]

rs12255372

GT

Intro

nic

281268

178(111ndash2

88)

0017

[22]

rs12255372

GT

Intro

nic

519547

137(106ndash

176)

c0014

[10]

DG10S478

STRCA

CAIntro

nic

282274

162(102ndash

257)

004

1[22]

TLR2

4q32

rs5743708

GA

RQ

321538

041

(004ndash

37)

040

[23]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

TLR4

9q33

rs4986790

AG

DG

321538

139(042ndash456)

058

[23]

rs4986791

CT

TI

321538

101(032ndash318

)098

[23]

TNF-120572

6p21

rs1800

629

-308GA

Upstre

am5148

076

(031

ndash185)

cn055

[20]

rs1800

629

-308GA

Upstre

am9587

466

(173ndash125)c

000

1[24]

rs1800

629

-308GA

Upstre

am25964

512

5(083ndash18

7)029

[25]

rs361525

-238GA

Upstre

am25964

515

7(107ndash

229

)0018

[25]

TSPA

N8LG

R512q14ndash

q21

rs7961581

CT

Intergenic

868504

093

(073ndash117)

e0516

[8]

TXNIP

1q21

rs7211

CT

31015840UTR

623969

097

(082ndash114)

067

[18]

UBQ

LNL

11p15

rs979752

CT

Upstre

am868504

104(084ndash

130)

e070

[8]

Chromchrom

osom

eRisk

alleles

arem

arkedin

bold119899

a 119899b Samplefor

casesa

ndcontrols

respectiv

elycCon

ventionalO

R(unadjusted)

was

assessed

byus

from

alleleor

geno

type

frequ

encies

repo

rteddLargest119899

was

registe

red

e Testw

ithou

tancestrycorrectio

nwas

consideredfCom

bineddatasetswerer

egisteredgRisk

was

onlyob

served

inno

nobese

T2Dpatients(OR=12

5119901=0009)

h OnlyGenotypes

ofT2

Dpatients


sedin

oura

nalysisiAssessm

entd

erived

from

thes

umof

T2Dpatients(ob

esea

ndno

nobese)

j Thea

utho

rsrepo

rted

aprotectore

ffectforthe

Aallele(

OR=065plt0001)but

inou

restim

ationwetoo

kas

referencethe

Aallelesin

ceitisthem

ostcom

mon

kSign

ificant

analysiswith

ancestr

ycorrectio

nwas

taken

l Associatio

nwas

onlyfoun

din

early

-onsetT2

D(O

R=13

9119901=0024)

mJustthe

popu

lationof

Guerrerowas

recorded

duetopo

ssibleoverlap

ping

ofthep

atientsfrom

theM

exicoCity

with

[10]nTh

eGallelew

asassessed

asris

kby

thea

utho

rsbut

inou

ranalysis

wetoo

ktheA

allelethes

ame

asthatin

previous

studies


Table2Analysis

ofSN

Psstu

died

bytwoor

moreg

roup

sinMexican

mestizos

Gene

dbSN

Ploc

Cases

(allele)

Con

trols

(allele)

Risk

allelefre

quency

()

OR(95

CI)

119901lowastvalue

Reference

Cases

Con

trols

CAPN

10rs3792267

1086

928

295

287

106(087ndash12

9)056

[11ndash13]

CAPN

10rs3842570

772

656

617

625

096

(078ndash12

0)074

[111314]

CAPN

10rs5030952

686

530

190

183

104(078ndash14

0)078

[1113]

CDKA

L1rs7754840

3092

3074

314

291

112(100ndash

125)

004

4[810]

HHEX

rs11118

752974

2448

628

617

105(094ndash

117)

043

[817]

IRS1

rs1801278

2326

2380

66

28

245

(183ndash328

)lt000

01[1219]

PPAR

Grs1801282

3492

3472

873

867

105(091ndash12

1)051

[812]

SLC3

0A4

rs13266634

2964

2448

763

730

119(105ndash13

5)000

5[817]

TCF7L2

rs7903146

3740

3042

178

141

132(116

ndash150)

lt000

01[81222]

TCF7L2

rs12255372

2476

2586

183

116

140(119

ndash165)

lt000

01[1222]

TNF-120572

rs1800

629

810

1560

115

62

196(145ndash264

)lt000

01[202425]


nchi-squ

aretest







Acknowledgments


References










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















dies

abou

ttype2

diabetes

cond

uctedin

Mexican

mestizos

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

ABCA

19q31

rs9282541

CT

RC

244202

250

(148ndash

424

)000

1[7]

rs2000

069

CT

Intro

nic

244202

108(082ndash14

2)c

058

[7]

rs2230806

GA

RK

244202

117(089ndash

155)

c027

[7]

rs2487037

CT

Intro

nic

244202

106(079ndash

143)

c071

[7]

rs3818689

GC

Intro

nic

244202

094

(052

ndash168)

c082

[7]

ADAM

TS9

3p14

rs46

07103

CT

Intro

nic

1027990

105(091ndash12

0)d

0521

[8]

ADRB

110q25

rs1801253

CG

RG

501552

079

(061ndash10

2)c

007

[9]

ADRB

38p11

rs4994

CT

WR

519547

169(137ndash

209

)c000

01[10]

rs4994

CT

WR

501552

134(110

ndash164)

c000

4[9]

ARHGE

F11

1q21

rs945508

GA

RH

868504

091

(076

ndash109)

e0319

[8]

CAPN

102q37

rs3792267

GA

Intro

nic

132112

097

(066ndash

142)

c086

[11]

rs3792267

GA

Intro

nic

719746

111(095ndash129)

cf020

[12]

rs3792267

GA

Intro

nic

211152

091

(066ndash

126)

056

[13]

rs3842570

2R3R

Intro

nic

132112

097

(068ndash14

0)c

089

[11]

rs3842570

2R3R

Intro

nic

4364

181(10

3ndash318)c

003

8[14

]rs3842570

2R3R

Intro

nic

211152

075

(055ndash10

2)006

[13]

rs5030952

CT

Intro

nic

132113

085

(056ndash

129)

c045

[11]

rs5030952

CT

Intro

nic

211152

135(089ndash

206)

016

[13]

rs2975760

TC

Intro

nic

134113

272

(116

ndash635)

0017

[11]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

CAPN

102q37

rs7607759

AG

TA

127110

227

(098ndash525)c

0051

[11]

CDC123CAM

K1D

10p13

rs12779790

AG

Intergenic

1027990

124(105ndash14

7)d

0013

[8]

CDKA

L16p

22

rs10946398

AC

Intro

nic

519547

109(091ndash13

2)c

0337

[10]

rs9465871

CT

Intro

nic

519547

104(085ndash12

6)c

0718

[10]

rs7754840

CG

Intro

nic

519547

108(089ndash

129)

c0438

[10]

rs7754840

CG

Intro

nic

1027990

113(098ndash13

0)dg

0081

[8]

CDKN

2A2B

9p21

rs10811661

CT

Upstre

am1027990

142(115

ndash175)

d000

1[8]

CRP

1q23

rs1130864

CT

31015840-U

TR166130

159(115

ndash222)

chi

000

5[15]

rs1205

GA

31015840-U

TR166130

082

(059ndash

114)

chi

024

[15]

rs2794521

AG

51015840-flanking

166130

197(115

ndash338)

chi

0012

[15]

rs3093062

GA

Prom

oter

166130

349

(098ndash

124)c

hi

0039

[15]

ELMO1

7p14

rs1345365

AG

Intro

nic

148269

137(102ndash

184)

chi

0035

[16]

ENPP

16q

23rs1044

498

AC

KQ

519547

094

(076

ndash116

)c0577

[10]

EXT2

11p11

rs3740

878

AG

Intro

nic

455234

083

(065ndash10

5)0054

[17]

FTO

16q12

rs8050136

AC

Intro

nic

868504

090

(074

ndash109)

e0278

[8]

rs993960

9AT

Intro

nic

519547

125(102ndash

154)

c0027

[10]

HHEX

10q23

rs5015480

CT

Upstre

am519547

096

(080ndash

114)

c0631

[10]

rs111

1875

CT

31015840-flanking

1027990

101(089ndash116

)d0859

[8]

rs111

1875

CT

31015840-flanking

455234

112(088ndash14

4)027

[17]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

HHEX

10q23

rs7923837

AG

31015840-flanking

868504

121(10

2ndash14

4)k

002

5[8]

HMOX1

22q12

rs2071749

AG

Prom

oter

614956

098

(084ndash

114)

c076

[18]

IGF2BP

23q27

rs44

02960

GT

Intro

nic

868504

124(101ndash15

3)j

004

2[8]

IRS1

2q36

rs1801278

GA

GR

719746

204

(141ndash296

)cf

lt000

1[12]

rs1801278

GA

GR

44444

4322

(199ndash

520

)000

1[19

]rs1801276

CG

PA

44444

4098

(072ndash13

2)083

[19]

rs3731594

GA

ND

44444

4083

(042ndash16

6)047

[19]

rs1801108

GC

RP

44444

410

7(085ndash13

4)040

[19]

JAZF

17p15

rs864745

TC

Intro

nic

868504

124(104ndash

147)

k0015

[8]

KCNJ11

11p15

rs5215

CT

VI

519547

103(087ndash12

3)c

0729

[10]

rs5210

AG

31015840-U

TR519547

103(086ndash

123)

c0764

[10]

rs5219

CT

EK

1027990

110(096ndash

126)

d0154

[8]

KCNQ1

11p15

rs2237892

CT

Intro

nic

868504

136(113

ndash164)

k000

1[8]

LEPR

1p31

rs1137100

AG

KR

519547

100(084ndash

121)

c092

[10]

LOC3

87761

11p12

rs7480010

AG

Intro

nic

455234

143(105ndash19

4)000

6[17]

LTA

6p21

rs909253

AG

Intro

nic

5148

198(102ndash

38)

c004

1[20]

MGE

A510q24

MGEA

5-14

AT

Intro

nic

271244

160(052

ndash486)

040

4[21]

NOTC

H2

1p11

rs10923931

GT

Intro

nic

1027990

104(082ndash13

2)d

0731

[8]

NQO1

16q22

rs1800566

CT

PS

623993

098

(085ndash113)

c076

[18]

NRF

22q31

rs2364723

CG

Intro

nic

625992

091

(079ndash

105)

c018

[18]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

NRF

22q31

rs6721961

CA

Prom

oter

623989

089

(074

ndash106)

c018

[8]

NXP

H1

7p22

rs757705

AG

Intro

nic

868504

125(105ndash14

8)k

001

[8]

PPAR

G3p25

rs1801282

CG

PA

719746

100(081ndash12

4)cf

100

[12]

rs1801282

CG

PA

1027990

110(090ndash

134)

d0342

[8]

rs17793693

AC

Intro

nic

519547

109(091ndash13

1)c

0329

[10]

RALG

PS2

1q25

rs2773080

AG

Intro

nic

868504

090

(074

ndash110

)e0315

[8]

RORA

15q22

rs7164773

CT

Intro

nic

868504

108(091ndash12

8)e

0357

[8]

SIRT

110q21

rs3758391

CT

Upstre

am519547

129(108ndash

154)

c000

4[10]

SLC3

0A4

8q24

rs13266634

CT

RW

455234

101(076ndash133

)092

[17]

rs13266634

CT

RW

1027990

122(105ndash14

1)d

000

9[8]

TCF7L2

10q25

rs7903146

CT

Intro

nic

868504

104(084ndash

128)

el0735

[8]

rs7903146

CT

Intro

nic

200200

184(105ndash320

)cm

004

[12]

rs7903146

CT

Intro

nic

519547

148(118

ndash186)

c000

07[10]

rs7903146

CT

Intro

nic

283271

125(092ndash17

0)016

[22]

rs12255372

GT

Intro

nic

200200

183(121ndash276)c

m000

6[12]

rs12255372

GT

Intro

nic

281268

178(111ndash2

88)

0017

[22]

rs12255372

GT

Intro

nic

519547

137(106ndash

176)

c0014

[10]

DG10S478

STRCA

CAIntro

nic

282274

162(102ndash

257)

004

1[22]

TLR2

4q32

rs5743708

GA

RQ

321538

041

(004ndash

37)

040

[23]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

TLR4

9q33

rs4986790

AG

DG

321538

139(042ndash456)

058

[23]

rs4986791

CT

TI

321538

101(032ndash318

)098

[23]

TNF-120572

6p21

rs1800

629

-308GA

Upstre

am5148

076

(031

ndash185)

cn055

[20]

rs1800

629

-308GA

Upstre

am9587

466

(173ndash125)c

000

1[24]

rs1800

629

-308GA

Upstre

am25964

512

5(083ndash18

7)029

[25]

rs361525

-238GA

Upstre

am25964

515

7(107ndash

229

)0018

[25]

TSPA

N8LG

R512q14ndash

q21

rs7961581

CT

Intergenic

868504

093

(073ndash117)

e0516

[8]

TXNIP

1q21

rs7211

CT

31015840UTR

623969

097

(082ndash114)

067

[18]

UBQ

LNL

11p15

rs979752

CT

Upstre

am868504

104(084ndash

130)

e070

[8]

Chromchrom

osom

eRisk

alleles

arem

arkedin

bold119899

a 119899b Samplefor

casesa

ndcontrols

respectiv

elycCon

ventionalO

R(unadjusted)

was

assessed

byus

from

alleleor

geno

type

frequ

encies

repo

rteddLargest119899

was

registe

red

e Testw

ithou

tancestrycorrectio

nwas

consideredfCom

bineddatasetswerer

egisteredgRisk

was

onlyob

served

inno

nobese

T2Dpatients(OR=12

5119901=0009)

h OnlyGenotypes

ofT2

Dpatients


sedin

oura

nalysisiAssessm

entd

erived

from

thes

umof

T2Dpatients(ob

esea

ndno

nobese)

j Thea

utho

rsrepo

rted

aprotectore

ffectforthe

Aallele(

OR=065plt0001)but

inou

restim

ationwetoo

kas

referencethe

Aallelesin

ceitisthem

ostcom

mon

kSign

ificant

analysiswith

ancestr

ycorrectio

nwas

taken

l Associatio

nwas

onlyfoun

din

early

-onsetT2

D(O

R=13

9119901=0024)

mJustthe

popu

lationof

Guerrerowas

recorded

duetopo

ssibleoverlap

ping

ofthep

atientsfrom

theM

exicoCity

with

[10]nTh

eGallelew

asassessed

asris

kby

thea

utho

rsbut

inou

ranalysis

wetoo

ktheA

allelethes

ame

asthatin

previous

studies


Table2Analysis

ofSN

Psstu

died

bytwoor

moreg

roup

sinMexican

mestizos

Gene

dbSN

Ploc

Cases

(allele)

Con

trols

(allele)

Risk

allelefre

quency

()

OR(95

CI)

119901lowastvalue

Reference

Cases

Con

trols

CAPN

10rs3792267

1086

928

295

287

106(087ndash12

9)056

[11ndash13]

CAPN

10rs3842570

772

656

617

625

096

(078ndash12

0)074

[111314]

CAPN

10rs5030952

686

530

190

183

104(078ndash14

0)078

[1113]

CDKA

L1rs7754840

3092

3074

314

291

112(100ndash

125)

004

4[810]

HHEX

rs11118

752974

2448

628

617

105(094ndash

117)

043

[817]

IRS1

rs1801278

2326

2380

66

28

245

(183ndash328

)lt000

01[1219]

PPAR

Grs1801282

3492

3472

873

867

105(091ndash12

1)051

[812]

SLC3

0A4

rs13266634

2964

2448

763

730

119(105ndash13

5)000

5[817]

TCF7L2

rs7903146

3740

3042

178

141

132(116

ndash150)

lt000

01[81222]

TCF7L2

rs12255372

2476

2586

183

116

140(119

ndash165)

lt000

01[1222]

TNF-120572

rs1800

629

810

1560

115

62

196(145ndash264

)lt000

01[202425]


nchi-squ

aretest







Acknowledgments


References










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

CAPN

102q37

rs7607759

AG

TA

127110

227

(098ndash525)c

0051

[11]

CDC123CAM

K1D

10p13

rs12779790

AG

Intergenic

1027990

124(105ndash14

7)d

0013

[8]

CDKA

L16p

22

rs10946398

AC

Intro

nic

519547

109(091ndash13

2)c

0337

[10]

rs9465871

CT

Intro

nic

519547

104(085ndash12

6)c

0718

[10]

rs7754840

CG

Intro

nic

519547

108(089ndash

129)

c0438

[10]

rs7754840

CG

Intro

nic

1027990

113(098ndash13

0)dg

0081

[8]

CDKN

2A2B

9p21

rs10811661

CT

Upstre

am1027990

142(115

ndash175)

d000

1[8]

CRP

1q23

rs1130864

CT

31015840-U

TR166130

159(115

ndash222)

chi

000

5[15]

rs1205

GA

31015840-U

TR166130

082

(059ndash

114)

chi

024

[15]

rs2794521

AG

51015840-flanking

166130

197(115

ndash338)

chi

0012

[15]

rs3093062

GA

Prom

oter

166130

349

(098ndash

124)c

hi

0039

[15]

ELMO1

7p14

rs1345365

AG

Intro

nic

148269

137(102ndash

184)

chi

0035

[16]

ENPP

16q

23rs1044

498

AC

KQ

519547

094

(076

ndash116

)c0577

[10]

EXT2

11p11

rs3740

878

AG

Intro

nic

455234

083

(065ndash10

5)0054

[17]

FTO

16q12

rs8050136

AC

Intro

nic

868504

090

(074

ndash109)

e0278

[8]

rs993960

9AT

Intro

nic

519547

125(102ndash

154)

c0027

[10]

HHEX

10q23

rs5015480

CT

Upstre

am519547

096

(080ndash

114)

c0631

[10]

rs111

1875

CT

31015840-flanking

1027990

101(089ndash116

)d0859

[8]

rs111

1875

CT

31015840-flanking

455234

112(088ndash14

4)027

[17]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

HHEX

10q23

rs7923837

AG

31015840-flanking

868504

121(10

2ndash14

4)k

002

5[8]

HMOX1

22q12

rs2071749

AG

Prom

oter

614956

098

(084ndash

114)

c076

[18]

IGF2BP

23q27

rs44

02960

GT

Intro

nic

868504

124(101ndash15

3)j

004

2[8]

IRS1

2q36

rs1801278

GA

GR

719746

204

(141ndash296

)cf

lt000

1[12]

rs1801278

GA

GR

44444

4322

(199ndash

520

)000

1[19

]rs1801276

CG

PA

44444

4098

(072ndash13

2)083

[19]

rs3731594

GA

ND

44444

4083

(042ndash16

6)047

[19]

rs1801108

GC

RP

44444

410

7(085ndash13

4)040

[19]

JAZF

17p15

rs864745

TC

Intro

nic

868504

124(104ndash

147)

k0015

[8]

KCNJ11

11p15

rs5215

CT

VI

519547

103(087ndash12

3)c

0729

[10]

rs5210

AG

31015840-U

TR519547

103(086ndash

123)

c0764

[10]

rs5219

CT

EK

1027990

110(096ndash

126)

d0154

[8]

KCNQ1

11p15

rs2237892

CT

Intro

nic

868504

136(113

ndash164)

k000

1[8]

LEPR

1p31

rs1137100

AG

KR

519547

100(084ndash

121)

c092

[10]

LOC3

87761

11p12

rs7480010

AG

Intro

nic

455234

143(105ndash19

4)000

6[17]

LTA

6p21

rs909253

AG

Intro

nic

5148

198(102ndash

38)

c004

1[20]

MGE

A510q24

MGEA

5-14

AT

Intro

nic

271244

160(052

ndash486)

040

4[21]

NOTC

H2

1p11

rs10923931

GT

Intro

nic

1027990

104(082ndash13

2)d

0731

[8]

NQO1

16q22

rs1800566

CT

PS

623993

098

(085ndash113)

c076

[18]

NRF

22q31

rs2364723

CG

Intro

nic

625992

091

(079ndash

105)

c018

[18]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

NRF

22q31

rs6721961

CA

Prom

oter

623989

089

(074

ndash106)

c018

[8]

NXP

H1

7p22

rs757705

AG

Intro

nic

868504

125(105ndash14

8)k

001

[8]

PPAR

G3p25

rs1801282

CG

PA

719746

100(081ndash12

4)cf

100

[12]

rs1801282

CG

PA

1027990

110(090ndash

134)

d0342

[8]

rs17793693

AC

Intro

nic

519547

109(091ndash13

1)c

0329

[10]

RALG

PS2

1q25

rs2773080

AG

Intro

nic

868504

090

(074

ndash110

)e0315

[8]

RORA

15q22

rs7164773

CT

Intro

nic

868504

108(091ndash12

8)e

0357

[8]

SIRT

110q21

rs3758391

CT

Upstre

am519547

129(108ndash

154)

c000

4[10]

SLC3

0A4

8q24

rs13266634

CT

RW

455234

101(076ndash133

)092

[17]

rs13266634

CT

RW

1027990

122(105ndash14

1)d

000

9[8]

TCF7L2

10q25

rs7903146

CT

Intro

nic

868504

104(084ndash

128)

el0735

[8]

rs7903146

CT

Intro

nic

200200

184(105ndash320

)cm

004

[12]

rs7903146

CT

Intro

nic

519547

148(118

ndash186)

c000

07[10]

rs7903146

CT

Intro

nic

283271

125(092ndash17

0)016

[22]

rs12255372

GT

Intro

nic

200200

183(121ndash276)c

m000

6[12]

rs12255372

GT

Intro

nic

281268

178(111ndash2

88)

0017

[22]

rs12255372

GT

Intro

nic

519547

137(106ndash

176)

c0014

[10]

DG10S478

STRCA

CAIntro

nic

282274

162(102ndash

257)

004

1[22]

TLR2

4q32

rs5743708

GA

RQ

321538

041

(004ndash

37)

040

[23]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

TLR4

9q33

rs4986790

AG

DG

321538

139(042ndash456)

058

[23]

rs4986791

CT

TI

321538

101(032ndash318

)098

[23]

TNF-120572

6p21

rs1800

629

-308GA

Upstre

am5148

076

(031

ndash185)

cn055

[20]

rs1800

629

-308GA

Upstre

am9587

466

(173ndash125)c

000

1[24]

rs1800

629

-308GA

Upstre

am25964

512

5(083ndash18

7)029

[25]

rs361525

-238GA

Upstre

am25964

515

7(107ndash

229

)0018

[25]

TSPA

N8LG

R512q14ndash

q21

rs7961581

CT

Intergenic

868504

093

(073ndash117)

e0516

[8]

TXNIP

1q21

rs7211

CT

31015840UTR

623969

097

(082ndash114)

067

[18]

UBQ

LNL

11p15

rs979752

CT

Upstre

am868504

104(084ndash

130)

e070

[8]

Chromchrom

osom

eRisk

alleles

arem

arkedin

bold119899

a 119899b Samplefor

casesa

ndcontrols

respectiv

elycCon

ventionalO

R(unadjusted)

was

assessed

byus

from

alleleor

geno

type

frequ

encies

repo

rteddLargest119899

was

registe

red

e Testw

ithou

tancestrycorrectio

nwas

consideredfCom

bineddatasetswerer

egisteredgRisk

was

onlyob

served

inno

nobese

T2Dpatients(OR=12

5119901=0009)

h OnlyGenotypes

ofT2

Dpatients


sedin

oura

nalysisiAssessm

entd

erived

from

thes

umof

T2Dpatients(ob

esea

ndno

nobese)

j Thea

utho

rsrepo

rted

aprotectore

ffectforthe

Aallele(

OR=065plt0001)but

inou

restim

ationwetoo

kas

referencethe

Aallelesin

ceitisthem

ostcom

mon

kSign

ificant

analysiswith

ancestr

ycorrectio

nwas

taken

l Associatio

nwas

onlyfoun

din

early

-onsetT2

D(O

R=13

9119901=0024)

mJustthe

popu

lationof

Guerrerowas

recorded

duetopo

ssibleoverlap

ping

ofthep

atientsfrom

theM

exicoCity

with

[10]nTh

eGallelew

asassessed

asris

kby

thea

utho

rsbut

inou

ranalysis

wetoo

ktheA

allelethes

ame

asthatin

previous

studies


Table2Analysis

ofSN

Psstu

died

bytwoor

moreg

roup

sinMexican

mestizos

Gene

dbSN

Ploc

Cases

(allele)

Con

trols

(allele)

Risk

allelefre

quency

()

OR(95

CI)

119901lowastvalue

Reference

Cases

Con

trols

CAPN

10rs3792267

1086

928

295

287

106(087ndash12

9)056

[11ndash13]

CAPN

10rs3842570

772

656

617

625

096

(078ndash12

0)074

[111314]

CAPN

10rs5030952

686

530

190

183

104(078ndash14

0)078

[1113]

CDKA

L1rs7754840

3092

3074

314

291

112(100ndash

125)

004

4[810]

HHEX

rs11118

752974

2448

628

617

105(094ndash

117)

043

[817]

IRS1

rs1801278

2326

2380

66

28

245

(183ndash328

)lt000

01[1219]

PPAR

Grs1801282

3492

3472

873

867

105(091ndash12

1)051

[812]

SLC3

0A4

rs13266634

2964

2448

763

730

119(105ndash13

5)000

5[817]

TCF7L2

rs7903146

3740

3042

178

141

132(116

ndash150)

lt000

01[81222]

TCF7L2

rs12255372

2476

2586

183

116

140(119

ndash165)

lt000

01[1222]

TNF-120572

rs1800

629

810

1560

115

62

196(145ndash264

)lt000

01[202425]


nchi-squ

aretest







Acknowledgments


References










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

HHEX

10q23

rs7923837

AG

31015840-flanking

868504

121(10

2ndash14

4)k

002

5[8]

HMOX1

22q12

rs2071749

AG

Prom

oter

614956

098

(084ndash

114)

c076

[18]

IGF2BP

23q27

rs44

02960

GT

Intro

nic

868504

124(101ndash15

3)j

004

2[8]

IRS1

2q36

rs1801278

GA

GR

719746

204

(141ndash296

)cf

lt000

1[12]

rs1801278

GA

GR

44444

4322

(199ndash

520

)000

1[19

]rs1801276

CG

PA

44444

4098

(072ndash13

2)083

[19]

rs3731594

GA

ND

44444

4083

(042ndash16

6)047

[19]

rs1801108

GC

RP

44444

410

7(085ndash13

4)040

[19]

JAZF

17p15

rs864745

TC

Intro

nic

868504

124(104ndash

147)

k0015

[8]

KCNJ11

11p15

rs5215

CT

VI

519547

103(087ndash12

3)c

0729

[10]

rs5210

AG

31015840-U

TR519547

103(086ndash

123)

c0764

[10]

rs5219

CT

EK

1027990

110(096ndash

126)

d0154

[8]

KCNQ1

11p15

rs2237892

CT

Intro

nic

868504

136(113

ndash164)

k000

1[8]

LEPR

1p31

rs1137100

AG

KR

519547

100(084ndash

121)

c092

[10]

LOC3

87761

11p12

rs7480010

AG

Intro

nic

455234

143(105ndash19

4)000

6[17]

LTA

6p21

rs909253

AG

Intro

nic

5148

198(102ndash

38)

c004

1[20]

MGE

A510q24

MGEA

5-14

AT

Intro

nic

271244

160(052

ndash486)

040

4[21]

NOTC

H2

1p11

rs10923931

GT

Intro

nic

1027990

104(082ndash13

2)d

0731

[8]

NQO1

16q22

rs1800566

CT

PS

623993

098

(085ndash113)

c076

[18]

NRF

22q31

rs2364723

CG

Intro

nic

625992

091

(079ndash

105)

c018

[18]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

NRF

22q31

rs6721961

CA

Prom

oter

623989

089

(074

ndash106)

c018

[8]

NXP

H1

7p22

rs757705

AG

Intro

nic

868504

125(105ndash14

8)k

001

[8]

PPAR

G3p25

rs1801282

CG

PA

719746

100(081ndash12

4)cf

100

[12]

rs1801282

CG

PA

1027990

110(090ndash

134)

d0342

[8]

rs17793693

AC

Intro

nic

519547

109(091ndash13

1)c

0329

[10]

RALG

PS2

1q25

rs2773080

AG

Intro

nic

868504

090

(074

ndash110

)e0315

[8]

RORA

15q22

rs7164773

CT

Intro

nic

868504

108(091ndash12

8)e

0357

[8]

SIRT

110q21

rs3758391

CT

Upstre

am519547

129(108ndash

154)

c000

4[10]

SLC3

0A4

8q24

rs13266634

CT

RW

455234

101(076ndash133

)092

[17]

rs13266634

CT

RW

1027990

122(105ndash14

1)d

000

9[8]

TCF7L2

10q25

rs7903146

CT

Intro

nic

868504

104(084ndash

128)

el0735

[8]

rs7903146

CT

Intro

nic

200200

184(105ndash320

)cm

004

[12]

rs7903146

CT

Intro

nic

519547

148(118

ndash186)

c000

07[10]

rs7903146

CT

Intro

nic

283271

125(092ndash17

0)016

[22]

rs12255372

GT

Intro

nic

200200

183(121ndash276)c

m000

6[12]

rs12255372

GT

Intro

nic

281268

178(111ndash2

88)

0017

[22]

rs12255372

GT

Intro

nic

519547

137(106ndash

176)

c0014

[10]

DG10S478

STRCA

CAIntro

nic

282274

162(102ndash

257)

004

1[22]

TLR2

4q32

rs5743708

GA

RQ

321538

041

(004ndash

37)

040

[23]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

TLR4

9q33

rs4986790

AG

DG

321538

139(042ndash456)

058

[23]

rs4986791

CT

TI

321538

101(032ndash318

)098

[23]

TNF-120572

6p21

rs1800

629

-308GA

Upstre

am5148

076

(031

ndash185)

cn055

[20]

rs1800

629

-308GA

Upstre

am9587

466

(173ndash125)c

000

1[24]

rs1800

629

-308GA

Upstre

am25964

512

5(083ndash18

7)029

[25]

rs361525

-238GA

Upstre

am25964

515

7(107ndash

229

)0018

[25]

TSPA

N8LG

R512q14ndash

q21

rs7961581

CT

Intergenic

868504

093

(073ndash117)

e0516

[8]

TXNIP

1q21

rs7211

CT

31015840UTR

623969

097

(082ndash114)

067

[18]

UBQ

LNL

11p15

rs979752

CT

Upstre

am868504

104(084ndash

130)

e070

[8]

Chromchrom

osom

eRisk

alleles

arem

arkedin

bold119899

a 119899b Samplefor

casesa

ndcontrols

respectiv

elycCon

ventionalO

R(unadjusted)

was

assessed

byus

from

alleleor

geno

type

frequ

encies

repo

rteddLargest119899

was

registe

red

e Testw

ithou

tancestrycorrectio

nwas

consideredfCom

bineddatasetswerer

egisteredgRisk

was

onlyob

served

inno

nobese

T2Dpatients(OR=12

5119901=0009)

h OnlyGenotypes

ofT2

Dpatients


sedin

oura

nalysisiAssessm

entd

erived

from

thes

umof

T2Dpatients(ob

esea

ndno

nobese)

j Thea

utho

rsrepo

rted

aprotectore

ffectforthe

Aallele(

OR=065plt0001)but

inou

restim

ationwetoo

kas

referencethe

Aallelesin

ceitisthem

ostcom

mon

kSign

ificant

analysiswith

ancestr

ycorrectio

nwas

taken

l Associatio

nwas

onlyfoun

din

early

-onsetT2

D(O

R=13

9119901=0024)

mJustthe

popu

lationof

Guerrerowas

recorded

duetopo

ssibleoverlap

ping

ofthep

atientsfrom

theM

exicoCity

with

[10]nTh

eGallelew

asassessed

asris

kby

thea

utho

rsbut

inou

ranalysis

wetoo

ktheA

allelethes

ame

asthatin

previous

studies


Table2Analysis

ofSN

Psstu

died

bytwoor

moreg

roup

sinMexican

mestizos

Gene

dbSN

Ploc

Cases

(allele)

Con

trols

(allele)

Risk

allelefre

quency

()

OR(95

CI)

119901lowastvalue

Reference

Cases

Con

trols

CAPN

10rs3792267

1086

928

295

287

106(087ndash12

9)056

[11ndash13]

CAPN

10rs3842570

772

656

617

625

096

(078ndash12

0)074

[111314]

CAPN

10rs5030952

686

530

190

183

104(078ndash14

0)078

[1113]

CDKA

L1rs7754840

3092

3074

314

291

112(100ndash

125)

004

4[810]

HHEX

rs11118

752974

2448

628

617

105(094ndash

117)

043

[817]

IRS1

rs1801278

2326

2380

66

28

245

(183ndash328

)lt000

01[1219]

PPAR

Grs1801282

3492

3472

873

867

105(091ndash12

1)051

[812]

SLC3

0A4

rs13266634

2964

2448

763

730

119(105ndash13

5)000

5[817]

TCF7L2

rs7903146

3740

3042

178

141

132(116

ndash150)

lt000

01[81222]

TCF7L2

rs12255372

2476

2586

183

116

140(119

ndash165)

lt000

01[1222]

TNF-120572

rs1800

629

810

1560

115

62

196(145ndash264

)lt000

01[202425]


nchi-squ

aretest







Acknowledgments


References










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

NRF

22q31

rs6721961

CA

Prom

oter

623989

089

(074

ndash106)

c018

[8]

NXP

H1

7p22

rs757705

AG

Intro

nic

868504

125(105ndash14

8)k

001

[8]

PPAR

G3p25

rs1801282

CG

PA

719746

100(081ndash12

4)cf

100

[12]

rs1801282

CG

PA

1027990

110(090ndash

134)

d0342

[8]

rs17793693

AC

Intro

nic

519547

109(091ndash13

1)c

0329

[10]

RALG

PS2

1q25

rs2773080

AG

Intro

nic

868504

090

(074

ndash110

)e0315

[8]

RORA

15q22

rs7164773

CT

Intro

nic

868504

108(091ndash12

8)e

0357

[8]

SIRT

110q21

rs3758391

CT

Upstre

am519547

129(108ndash

154)

c000

4[10]

SLC3

0A4

8q24

rs13266634

CT

RW

455234

101(076ndash133

)092

[17]

rs13266634

CT

RW

1027990

122(105ndash14

1)d

000

9[8]

TCF7L2

10q25

rs7903146

CT

Intro

nic

868504

104(084ndash

128)

el0735

[8]

rs7903146

CT

Intro

nic

200200

184(105ndash320

)cm

004

[12]

rs7903146

CT

Intro

nic

519547

148(118

ndash186)

c000

07[10]

rs7903146

CT

Intro

nic

283271

125(092ndash17

0)016

[22]

rs12255372

GT

Intro

nic

200200

183(121ndash276)c

m000

6[12]

rs12255372

GT

Intro

nic

281268

178(111ndash2

88)

0017

[22]

rs12255372

GT

Intro

nic

519547

137(106ndash

176)

c0014

[10]

DG10S478

STRCA

CAIntro

nic

282274

162(102ndash

257)

004

1[22]

TLR2

4q32

rs5743708

GA

RQ

321538

041

(004ndash

37)

040

[23]


Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

TLR4

9q33

rs4986790

AG

DG

321538

139(042ndash456)

058

[23]

rs4986791

CT

TI

321538

101(032ndash318

)098

[23]

TNF-120572

6p21

rs1800

629

-308GA

Upstre

am5148

076

(031

ndash185)

cn055

[20]

rs1800

629

-308GA

Upstre

am9587

466

(173ndash125)c

000

1[24]

rs1800

629

-308GA

Upstre

am25964

512

5(083ndash18

7)029

[25]

rs361525

-238GA

Upstre

am25964

515

7(107ndash

229

)0018

[25]

TSPA

N8LG

R512q14ndash

q21

rs7961581

CT

Intergenic

868504

093

(073ndash117)

e0516

[8]

TXNIP

1q21

rs7211

CT

31015840UTR

623969

097

(082ndash114)

067

[18]

UBQ

LNL

11p15

rs979752

CT

Upstre

am868504

104(084ndash

130)

e070

[8]

Chromchrom

osom

eRisk

alleles

arem

arkedin

bold119899

a 119899b Samplefor

casesa

ndcontrols

respectiv

elycCon

ventionalO

R(unadjusted)

was

assessed

byus

from

alleleor

geno

type

frequ

encies

repo

rteddLargest119899

was

registe

red

e Testw

ithou

tancestrycorrectio

nwas

consideredfCom

bineddatasetswerer

egisteredgRisk

was

onlyob

served

inno

nobese

T2Dpatients(OR=12

5119901=0009)

h OnlyGenotypes

ofT2

Dpatients


sedin

oura

nalysisiAssessm

entd

erived

from

thes

umof

T2Dpatients(ob

esea

ndno

nobese)

j Thea

utho

rsrepo

rted

aprotectore

ffectforthe

Aallele(

OR=065plt0001)but

inou

restim

ationwetoo

kas

referencethe

Aallelesin

ceitisthem

ostcom

mon

kSign

ificant

analysiswith

ancestr

ycorrectio

nwas

taken

l Associatio

nwas

onlyfoun

din

early

-onsetT2

D(O

R=13

9119901=0024)

mJustthe

popu

lationof

Guerrerowas

recorded

duetopo

ssibleoverlap

ping

ofthep

atientsfrom

theM

exicoCity

with

[10]nTh

eGallelew

asassessed

asris

kby

thea

utho

rsbut

inou

ranalysis

wetoo

ktheA

allelethes

ame

asthatin

previous

studies


Table2Analysis

ofSN

Psstu

died

bytwoor

moreg

roup

sinMexican

mestizos

Gene

dbSN

Ploc

Cases

(allele)

Con

trols

(allele)

Risk

allelefre

quency

()

OR(95

CI)

119901lowastvalue

Reference

Cases

Con

trols

CAPN

10rs3792267

1086

928

295

287

106(087ndash12

9)056

[11ndash13]

CAPN

10rs3842570

772

656

617

625

096

(078ndash12

0)074

[111314]

CAPN

10rs5030952

686

530

190

183

104(078ndash14

0)078

[1113]

CDKA

L1rs7754840

3092

3074

314

291

112(100ndash

125)

004

4[810]

HHEX

rs11118

752974

2448

628

617

105(094ndash

117)

043

[817]

IRS1

rs1801278

2326

2380

66

28

245

(183ndash328

)lt000

01[1219]

PPAR

Grs1801282

3492

3472

873

867

105(091ndash12

1)051

[812]

SLC3

0A4

rs13266634

2964

2448

763

730

119(105ndash13

5)000

5[817]

TCF7L2

rs7903146

3740

3042

178

141

132(116

ndash150)

lt000

01[81222]

TCF7L2

rs12255372

2476

2586

183

116

140(119

ndash165)

lt000

01[1222]

TNF-120572

rs1800

629

810

1560

115

62

196(145ndash264

)lt000

01[202425]


nchi-squ

aretest







Acknowledgments


References










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table1Con

tinued

Gene

Chrom

dbSN

Ploc

Change

Effect

119899a 119899b

OR(95

CI)

119901Re

ference

TLR4

9q33

rs4986790

AG

DG

321538

139(042ndash456)

058

[23]

rs4986791

CT

TI

321538

101(032ndash318

)098

[23]

TNF-120572

6p21

rs1800

629

-308GA

Upstre

am5148

076

(031

ndash185)

cn055

[20]

rs1800

629

-308GA

Upstre

am9587

466

(173ndash125)c

000

1[24]

rs1800

629

-308GA

Upstre

am25964

512

5(083ndash18

7)029

[25]

rs361525

-238GA

Upstre

am25964

515

7(107ndash

229

)0018

[25]

TSPA

N8LG

R512q14ndash

q21

rs7961581

CT

Intergenic

868504

093

(073ndash117)

e0516

[8]

TXNIP

1q21

rs7211

CT

31015840UTR

623969

097

(082ndash114)

067

[18]

UBQ

LNL

11p15

rs979752

CT

Upstre

am868504

104(084ndash

130)

e070

[8]

Chromchrom

osom

eRisk

alleles

arem

arkedin

bold119899

a 119899b Samplefor

casesa

ndcontrols

respectiv

elycCon

ventionalO

R(unadjusted)

was

assessed

byus

from

alleleor

geno

type

frequ

encies

repo

rteddLargest119899

was

registe

red

e Testw

ithou

tancestrycorrectio

nwas

consideredfCom

bineddatasetswerer

egisteredgRisk

was

onlyob

served

inno

nobese

T2Dpatients(OR=12

5119901=0009)

h OnlyGenotypes

ofT2

Dpatients


sedin

oura

nalysisiAssessm

entd

erived

from

thes

umof

T2Dpatients(ob

esea

ndno

nobese)

j Thea

utho

rsrepo

rted

aprotectore

ffectforthe

Aallele(

OR=065plt0001)but

inou

restim

ationwetoo

kas

referencethe

Aallelesin

ceitisthem

ostcom

mon

kSign

ificant

analysiswith

ancestr

ycorrectio

nwas

taken

l Associatio

nwas

onlyfoun

din

early

-onsetT2

D(O

R=13

9119901=0024)

mJustthe

popu

lationof

Guerrerowas

recorded

duetopo

ssibleoverlap

ping

ofthep

atientsfrom

theM

exicoCity

with

[10]nTh

eGallelew

asassessed

asris

kby

thea

utho

rsbut

inou

ranalysis

wetoo

ktheA

allelethes

ame

asthatin

previous

studies


Table2Analysis

ofSN

Psstu

died

bytwoor

moreg

roup

sinMexican

mestizos

Gene

dbSN

Ploc

Cases

(allele)

Con

trols

(allele)

Risk

allelefre

quency

()

OR(95

CI)

119901lowastvalue

Reference

Cases

Con

trols

CAPN

10rs3792267

1086

928

295

287

106(087ndash12

9)056

[11ndash13]

CAPN

10rs3842570

772

656

617

625

096

(078ndash12

0)074

[111314]

CAPN

10rs5030952

686

530

190

183

104(078ndash14

0)078

[1113]

CDKA

L1rs7754840

3092

3074

314

291

112(100ndash

125)

004

4[810]

HHEX

rs11118

752974

2448

628

617

105(094ndash

117)

043

[817]

IRS1

rs1801278

2326

2380

66

28

245

(183ndash328

)lt000

01[1219]

PPAR

Grs1801282

3492

3472

873

867

105(091ndash12

1)051

[812]

SLC3

0A4

rs13266634

2964

2448

763

730

119(105ndash13

5)000

5[817]

TCF7L2

rs7903146

3740

3042

178

141

132(116

ndash150)

lt000

01[81222]

TCF7L2

rs12255372

2476

2586

183

116

140(119

ndash165)

lt000

01[1222]

TNF-120572

rs1800

629

810

1560

115

62

196(145ndash264

)lt000

01[202425]


nchi-squ

aretest







Acknowledgments


References










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table2Analysis

ofSN

Psstu

died

bytwoor

moreg

roup

sinMexican

mestizos

Gene

dbSN

Ploc

Cases

(allele)

Con

trols

(allele)

Risk

allelefre

quency

()

OR(95

CI)

119901lowastvalue

Reference

Cases

Con

trols

CAPN

10rs3792267

1086

928

295

287

106(087ndash12

9)056

[11ndash13]

CAPN

10rs3842570

772

656

617

625

096

(078ndash12

0)074

[111314]

CAPN

10rs5030952

686

530

190

183

104(078ndash14

0)078

[1113]

CDKA

L1rs7754840

3092

3074

314

291

112(100ndash

125)

004

4[810]

HHEX

rs11118

752974

2448

628

617

105(094ndash

117)

043

[817]

IRS1

rs1801278

2326

2380

66

28

245

(183ndash328

)lt000

01[1219]

PPAR

Grs1801282

3492

3472

873

867

105(091ndash12

1)051

[812]

SLC3

0A4

rs13266634

2964

2448

763

730

119(105ndash13

5)000

5[817]

TCF7L2

rs7903146

3740

3042

178

141

132(116

ndash150)

lt000

01[81222]

TCF7L2

rs12255372

2476

2586

183

116

140(119

ndash165)

lt000

01[1222]

TNF-120572

rs1800

629

810

1560

115

62

196(145ndash264

)lt000

01[202425]


nchi-squ

aretest







Acknowledgments


References










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






















Acknowledgments


References










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Documents

ReviewArticle Genetic Epidemiology of Type 2 Diabetes in …downloads.hindawi.com/journals/bmri/2017/3937893.pdf · 2019. 7. 30. · ELMO1 7p14 rs1345365 A/ G Intronic 148;269. (.–.)