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ELECTRONIC ABSTRACTS FROM AROUND THE WORLD Click on citations to link these articles and additional papers of interest. It’s All in the Genes Parkes M, Barrett JC, Prescott NJ, et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci con- tribute to Crohn’s disease susceptibility. Nature Genetics 2007; 39:830 – 832. Van Heel DA, Franke L, Hunt KA, et al. A genome-wide asso- ciation study for Celiac disease identifies risk variants in the region harboring IL2 and IL21 Nature Genetics 2007;39:827– 829. Summary. New approaches to identification of the genetic basis of common diseases have been made possi- ble by the mapping of the DNA sequence of the human genome and subsequent discovery of genetic variants at defined locations along the chromosomes. Many variant single nucleotide polymorphisms (SNPs) are inherited together in blocks creating haplotypes. A map of these haplotypes (the HapMap) has been generated which has reduced the number of SNP markers needed to define genetic associations with a given trait or disease. Parkes et al mapped 500,000 SNPs in each of 1748 Crohn’s disease cases and in 2938 controls. Strong association was found to several genes already known to be linked to Crohn’s disease; namely, NOD2(CARD15), IL23R, and ATG16L1. Multiple new gene loci were identified and replicated in an independent set of patients and controls. These in- clude IRGM on Chr5q33, IL12B also on Chr5p33, NKX2-3 on Chr10q24, and PTPN2 on Chr18p11. Inter- estingly, both the ATG16L1 and IRGM genes appear to be involved in autophagy. Autophagy involves the catabo- lism and recycling of intracellular components via lyso- somes and appears to be involved in resistance to some intracellular microbes. These genetic studies indicate that autophagy plays a previously unsuspected role in Crohn’s disease. Van Heel et al tested 310,605 SNP markers in each of 778 individuals with celiac disease, and in 1422 controls from the U.K. The strongest gene association was with the DQ2 locus. Significant association was found and replicated for a gene locus on Chr4q27. This locus has genes encoding interleukin 2 and interleukin 21, genes not previously linked to Crohn’s disease. Editor’s comment. Rapid advances in technology have made feasible this type of unbiased analysis of the genetic basis of disease. The whole genome association approach is being applied to many diseases with the results hitting newspapers regularly. The power of these advances is that disease susceptibility genes, even those of modest effects, are being unequivocally identified, allow- ing investigators to focus their studies on genes and gene products known to play a role. Some of the genes iden- tified are revealing pathways, such as autophagy in IBD, that were not previously considered to be involved. The challenge is to understand the mechanisms involved, and in that sense, the identification of the contributing genes is only a beginning. Although this process will take time, and there is no near-term clinical application, these stud- ies will undoubtedly translate to the clinic in the future. Stay tuned. Additional Papers of Interest MacLeod JB, Lefton J, Houghton D, et al. Prospective randomized control trial of intermittent versus continu- ous gastric feeds for critically ill trauma patients. J Trauma 2007;63:57– 61. Spada C, Shah, S, Riccioni ME, et al. Video capsule endoscopy in patients with known or suspected small bowel stricture previously tested with the dissolving pa- tency capsule. J Clin Gastroenterol 2007;41:576 –582. Kalambokis G, Manousou P, Vibhakom S, et al.Tran- sjugular liver biopsy – indications, adequacy, quality of specimens, and complications a systematic review. J Hepatol 2007;47:284 –294. Arebi N, Swain D, Suzuki N, et al. Endoscopic mucosal resection of 161 cases of large sessile or flat colorectal polyps. Scand J Gastroenterol 2007;42:859 – 866. Larsson SC, Wolk A. Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer 2007; Aug 14 [Epub ahead of print] Benito-Garcia E, Michaud K, Wolfe F. The effect of low-dose aspirin on the decreased risk of development of dyspepsia and gastrointestinal ulcers associated to cyclo- oxygenase-2 selective inhibitors. J Rheumatol 2007;34: 1765–1769. Brown CJ, Dubreuil D, Santoro L, et al. Lateral internal sphincterotomy is superior to topical nitroglycerin for healing chronic annals fissure and does not compromise long-term fecal continence: six-year follow-up of a mul- ticenter, randomized, controlled trial. Dis Colon Rectum 2007;50:442– 448. Polkowski M, Regula J, Tilszer A, Butruk E. Endo- scopic ultrasound versus endoscopic retrograde cholan- giography for patients with intermediate probability of bile duct stones: a randomized trial comparing two man- agement strategies. Endoscopy 2007;39:296 –303. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2007;5:e44

Electronic Abstracts from Around the World

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CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2007;5:e44

LECTRONIC ABSTRACTS FROM AROUNDHE WORLD

Click on citations to link these articles and additional papers of interest.

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It’s All in the Genesarkes M, Barrett JC, Prescott NJ, et al. Sequence variants in theutophagy gene IRGM and multiple other replicating loci con-ribute to Crohn’s disease susceptibility. Nature Genetics 2007;9:830 – 832.an Heel DA, Franke L, Hunt KA, et al. A genome-wide asso-iation study for Celiac disease identifies risk variants in theegion harboring IL2 and IL21 Nature Genetics 2007;39:827–29.

Summary. New approaches to identification of theenetic basis of common diseases have been made possi-le by the mapping of the DNA sequence of the humanenome and subsequent discovery of genetic variants atefined locations along the chromosomes. Many variantingle nucleotide polymorphisms (SNPs) are inheritedogether in blocks creating haplotypes. A map of theseaplotypes (the HapMap) has been generated which haseduced the number of SNP markers needed to defineenetic associations with a given trait or disease. Parkes etl mapped 500,000 SNPs in each of 1748 Crohn’s diseaseases and in 2938 controls. Strong association was foundo several genes already known to be linked to Crohn’sisease; namely, NOD2(CARD15), IL23R, and ATG16L1.ultiple new gene loci were identified and replicated in

n independent set of patients and controls. These in-lude IRGM on Chr5q33, IL12B also on Chr5p33,KX2-3 on Chr10q24, and PTPN2 on Chr18p11. Inter-

stingly, both the ATG16L1 and IRGM genes appear to benvolved in autophagy. Autophagy involves the catabo-ism and recycling of intracellular components via lyso-omes and appears to be involved in resistance to somentracellular microbes. These genetic studies indicate thatutophagy plays a previously unsuspected role in Crohn’sisease. Van Heel et al tested 310,605 SNP markers inach of 778 individuals with celiac disease, and in 1422ontrols from the U.K. The strongest gene associationas with the DQ2 locus. Significant association was

ound and replicated for a gene locus on Chr4q27. Thisocus has genes encoding interleukin 2 and interleukin 21,enes not previously linked to Crohn’s disease.

Editor’s comment. Rapid advances in technologyave made feasible this type of unbiased analysis of theenetic basis of disease. The whole genome associationpproach is being applied to many diseases with theesults hitting newspapers regularly. The power of thesedvances is that disease susceptibility genes, even those of

odest effects, are being unequivocally identified, allow- a

ng investigators to focus their studies on genes and generoducts known to play a role. Some of the genes iden-ified are revealing pathways, such as autophagy in IBD,hat were not previously considered to be involved. Thehallenge is to understand the mechanisms involved, andn that sense, the identification of the contributing geness only a beginning. Although this process will take time,nd there is no near-term clinical application, these stud-es will undoubtedly translate to the clinic in the future.tay tuned.

dditional Papers of Interest

MacLeod JB, Lefton J, Houghton D, et al. Prospectiveandomized control trial of intermittent versus continu-us gastric feeds for critically ill trauma patients.Trauma 2007;63:57– 61.

Spada C, Shah, S, Riccioni ME, et al. Video capsulendoscopy in patients with known or suspected smallowel stricture previously tested with the dissolving pa-ency capsule. J Clin Gastroenterol 2007;41:576 –582.

Kalambokis G, Manousou P, Vibhakom S, et al.Tran-jugular liver biopsy – indications, adequacy, quality ofpecimens, and complications – a systematic review.Hepatol 2007;47:284 –294.Arebi N, Swain D, Suzuki N, et al. Endoscopic mucosal

esection of 161 cases of large sessile or flat colorectalolyps. Scand J Gastroenterol 2007;42:859 – 866.

Larsson SC, Wolk A. Overweight, obesity and risk ofiver cancer: a meta-analysis of cohort studies. Br J Cancer007; Aug 14 [Epub ahead of print]

Benito-Garcia E, Michaud K, Wolfe F. The effect ofow-dose aspirin on the decreased risk of development ofyspepsia and gastrointestinal ulcers associated to cyclo-xygenase-2 selective inhibitors. J Rheumatol 2007;34:765–1769.

Brown CJ, Dubreuil D, Santoro L, et al. Lateral internalphincterotomy is superior to topical nitroglycerin forealing chronic annals fissure and does not compromise

ong-term fecal continence: six-year follow-up of a mul-icenter, randomized, controlled trial. Dis Colon Rectum007;50:442– 448.

Polkowski M, Regula J, Tilszer A, Butruk E. Endo-copic ultrasound versus endoscopic retrograde cholan-iography for patients with intermediate probability ofile duct stones: a randomized trial comparing two man-

gement strategies. Endoscopy 2007;39:296 –303.