The Secret to Long Life is Personalized Nutrition - Nutrigenetic Testing and your health

The secret of long life is personalized

nutrition

Marie Vranceanu,Nutritionist, Biologist, Ketogenic Diet & Nutrigenetics Specialist

Dr. Maria Vranceanu, Nutritionist , Biologist, Ketogenic Diet & Nutrigenetics Specialist


nutrition


Dr. Maria Vranceanu, Nutritionist , Biologist, Ketogenic Diet & Nutrigenetics Specialist Milan


nutrition



Cluj

The secret of long life is personalized nutrition

What is Nutrigenetics?

Nutrigenomics studies how individual differences in genes influence the body's response to diet and nutrition. With modern genomic data, severe gene mutations with less severe effects are being explored to determine whether dietary practices can be more closely personalized to individual genetic profiles.



Nutrigenetics: the science of the effect of genetic variation on dietary response Nutrigenomics: the science of the effect of nutrients and bioactive components on gene expression

Aim is to obtain a better understanding of nutrient/gene interactions depending on the genotype

Ultimate goal is to develop personalized nutrition strategies for optimal health and diseaseDr. Maria Vranceanu, Nutritionist , Biologist, Ketogenic Diet & Nutrigenetics Specialist



Human genome project Craig Venter &

secventierea genomului uman



In mod oarecum ironic nutrigenomica reia o ideea antica: Hippocrate: mancarea sa iti fie medicament



Ingredientele din alimente pot influenta in mod direct sau indirect (prin sisteme de semnalizare) transcriptia informatiei codificata in ADN nostru si pot determina schimbari ale acestei informatii in sens pozitiv sau negativ



Cu proiectul Human Genome au fost identificate peste 2000 gene , Craig Venter spunea 22.333, mai mult decat gaina si mai putin decat vita de vie



Fiecare gena codifica pentru una sau mai multe proteine din organism Aceste peste 20000 gene reprezinta doar 2% din genomul uman98% este partea non coding si careia inca nu i s-a atribuit o functie



Cum pot influenta alimentele genele

noastre si digestia?



Milk and Lactose intolerance



LCT gene SNP

SNPs) have been associated with lactase expressionC−13910 (C at position -13910 upstream of the gene LCT) and G−22018 (G at position -22018) are related to lactase nonpersistence

While T−13910 and A−22018 are related to lactase persistence



Lactose Intolerance – 4 kindsPrimary lactase deficiency, Secondary lactase deficiency Developmental lactase deficiency Congenital lactase deficiency



A single nucleotide polymorphism or simple nucleotide polymorphism, often abbreviated to just SNP(pronounced snip; plural snips), is a variation in a single nucleotide which may occur at some specific position in the genome, where each variation is present to some appreciable degree within a population (e.g.>1%).

https://en.wikipedia.org/wiki/Nucleotide

https://en.wikipedia.org/wiki/Genome



LCT

CCCTTT



Genetics of alcohol metabolismAlcohol metabolism occurs mainly via hepatic

oxidation and is governed by the catalytic properties of the alcohol-metabolizing enzymes,

alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH2). •

Genetic polymorphisms in ADH1B and ALDH2 ,

and ethnic differences in the prevalence of these polymorphisms, result in increased variation in alcohol metabolism among individuals. •



Genetics of alcohol metabolismPolymorphisms in ADH1B result in variants that code for

isozymes that tend to show a faster rate of alcohol metabolism,

ALDH2*2 polymorphism results in a “deficient” form of ALDH2 that causes an accumulation of acetaldehyde and

its associated physiological effects. •

ADH and ALDH polymorphisms are also associated with a protective effect on the development of alcoholism.

The allele frequencies of ADH1B*2 , ADH1B*3 , and ALDH2*2 are significantly lower in individuals diagnosed

with alcohol dependence compared to controls.



Genetics of alcohol metabolismFurther evaluation of the factors, both genetic and environmental, regulating the rates of alcohol and acetaldehyde

metabolism, will help improve our understanding of the metabolic basis

and consequences of alcohol’s effects, including the risk and consequences

of alcohol-related organ damage, developmental problems, as well as

alcohol dependence.



The efficiency of our salivaAMY1 provides the information for the body to make amylase in saliva, which is used to process carbohydrates.

People with more of this enzyme seem to gain more nutrition from bread and vegetables — so much so that those in the top 10 per cent for the number of AMY1 "copy number variations" are eight times more likely to be obese than those in the bottom.



The efficiency of our saliva"People with extra copies of this amylase gene are able more efficiently to digest carbohydrates and starch," said Professor Spector. "By a small percentage difference, over time they put on more calories than those who have less copies — even if given the same food.”



Genetics of obesity



Genetics of obesity Obesity, defined as an excess fat mass, is a complex and multifactorial disease resulting from the interaction of numerous environmental and genetic factors. It is characterized by a wide phenotypic heterogeneity.The severity of obesity will be thus determined by the impact of environment on the genetic background of each individual.



Genetics of obesity Phenotype - (from Greek phainein, meaning "to show", and typos, meaning "type") is the composite of an organism's observable characteristics or traits, such as its morphology, development, biochemical or physiological properties, phenology, behavior, and products of behavior (such as a bird's nest). A phenotype results from the expression of an organism's genes as well as the influence of environmental factors and the interactions between the two.

The genotype of an organism is the inherited instructions it carries within its genome.

https://en.wikipedia.org/wiki/Greek_language

https://en.wikipedia.org/wiki/Organism

https://en.wikipedia.org/wiki/Trait_(biology)

https://en.wikipedia.org/wiki/Morphology_(biology)

https://en.wikipedia.org/wiki/Developmental_biology

https://en.wikipedia.org/wiki/Phenology

https://en.wikipedia.org/wiki/Behavior

https://en.wikipedia.org/wiki/Genotype

https://en.wikipedia.org/wiki/Genome



Genetics of obesity Several clinical presentations are

described in obesity depending on the involved genes:

Monogenic obesity Syndromic obesity



Genetics of obesity Monogenic obesitydescribed as rare and severe early-onset

obesity associated with endocrine disorders. There are mainly due to mutations in genes of the leptin/melanocortin axis involved in food intake regulation (genes of leptin ( LEP)

and its receptor ( LEPR), proopiomelanocortin ( POMC), proconvertase 1 ( PC1), etc).



Genetics of obesity Syndromic obesity

corresponding to obesity associated with others genetic syndromes.

Patients are clinically severely obese and additionally distinguished by mental retardation, dysmorphic features and organ-specific developmental abnormalities.

Prader-Willi and Bardet-Biedl syndromes are the 2 most frequent.




Leptin Deficiency Mutations in the human genes coding for LEP [3–5] and LEPR [6, 7] lead to rapid and dramatic increase in weight since the first months of life, as illustrated by the weight curve of LEPR deficient subjects Evaluating body composition in some LEPR mutation carriers show a large amount of total body fat mass (>50%) but resting energy expenditure remains related to the level of body corpulence. Feeding behaviour is characterized by major hyperphagia and ravenous hunger.




Surprisingly, one LEP deficient Austrian girl has been recently described with more moderate obesity (BMI 31.5 kg/m2 ), despite an increased consumption of calories in a test meal [11].

The phenotype was explained by extremely low daily calorie intake.

In that specific case, the parents’ role was determinant by providing a favourable environment with vigorous control of the patient’s eating behaviour from early infancy onward.




However, despite this particular case, severe early-onset obesity with major hyperphagia is recognized as a main clinical presentation of LEP or LEPR deficiency.

Associated to the severe early-onset obesity with major hyperphagia, hypogonadotrophic hypogonadism and thyrotrophic insufficiencies complete the phenotype.

In LEP deficient subjects, it was described a high rate of infection, particularly recurrent respiratory tract infections, associated with a deficiency in T cell number and function



Genetics of obesity Diagnosis Genetic Testing of

Monogenic Obesity In case of clinical situation suggesting a monogenic obesity (severe early-onset obesity associated to endocrine anomalies and potentially consanguineous parents), direct sequencing of the candidate gene ( LEP, LEPR, POMC, etc.) is necessary for diagnosis confirmation. It will detect homozygous or compound heterozygous mutation responsible for an interruption of the leptin-melanocortin axis.

Family members are needed to be tested for segregation analysis and to evaluate the risk of recurrence.



Genetics of obesity Diagnosis Genetic Testing of

Monogenic Obesity

LEP/MCLEPR POMC -proopiomelanocortin PC1-proconvertasa 1

Prader-Willi and Bardet-Biedl



Genetics of obesity Polygenic obesity

113 candidate genesADRB1(adrenoreceptor beta)

ADRB2, ADRB3 UCP1(uncoupling protein1)

UCP2, UCP3

PPARG(Peroxisome Proliferator-Activated Receptor Gamma) PPARD,

ACDC(adiponectin gene) TNF alpha

IL6 AGRP (agouti related neuropeptide)

GHLR (Growth Hormone-Releasing Peptide) GNB3 (guanine nucleotide binding protein) , etc.



Genetics of obesity Genes encoding factors

implicated in energy expenditure The adaptive thermogenesis in humans is closely related to the active mobilisation of lipids from fat tissues and demand special interest in relation to obesity. Central neural pathways responsible for the food intake and energy expenditure regulation are tightly interconnected.




implicated in energy expenditure The peripheral transmission of central commands to the fat stores is mediated by the sympathetic nervous system. b-adrenoceptor gene families (ADRB2, ADRB3, ADRB1) are intensively studied candidate genes in the obesity field for their participation in energy expenditure regulation.




implicated in energy expenditure The b2-adrenergic receptor gene (ADRB2) encodes a major lipolytic receptor protein in human fat cells.



Genetics of obesityTwo common polymorphisms of the ADRB2 gene, characterised by an amino acid replacement of arginine by glycine in codon 16 (Arg16Gly) and glutamine by glutamic acid in codon 27 (Gln27Glu), have been explored in several diseases such as hypertension and obesity2,15–18.

A relationship between the Arg16Gly polymorphism and an altered function of the ADBR2 has been reported leading to a decreased agonist sensitivity.



Genetics of obesity Gln27Glu variant was also found to be linked to obesity in some populations. In men, the 27Glu allele has been associated with increased BMI and subcutaneous fat and with elevated leptin and triglycerides levels

while in women, the 27Glu variant was reported to be linked to increased BMI




implicated in energy expenditure The b3-adrenergic receptor (ADRB3) protein plays a role in adipocyte metabolism mediating the rate of lipolysis in response to catecholamines and their agonists have potential anti-diabetes and anti-obesity properties2,19–22.

A common polymorphism in this gene, characterized by an amino acid replacement of tryptophan by arginine at position 64 (Trp64Arg), has been identified and may be linked to lower lipolytic activity and account for lipid accumulation in the adipose tissue.



Genetics of obesityA number of articles have reported the relationship between the Trp64Arg

variant of the ADRB3 and obesity-related phenotypes.




implicated in energy expenditure more than nine studies have shown a statistically significant association between BMI and the Trp64Arg polymorphism in a variety of populations from 134 to 856 subjects.



Genetics of obesity Several UCP2 gene variants have been described: •a G/A mutation in the promoter region 2866G/A, •a valine for alanine substitution at amino acid 55 in exon 4 (Ala55Val) and •a 45 base pair insertion/deletion in the untranslated region of exon 822,26,27.

The association between these polymorphisms of the UCP2 and various aspects of obesity have been intensively studied. From the literature, it seems that allele G in the promoter region of UCP2 increases obesity risk while it affords relative protection for type 2 diabetes



Genetics of obesity Gene variants in MC4R, SIRT1 and FTO are metabolic impairment in Caucasians.

FTO polymorphisms (rs1861868, rs1421085 and rs9939609) strong association with obesity



Genetics of obesity Gene implicate in adipogeneza

•PPARG •Polimorfism PRO12ALA asociat cu obezitate si diabet tip 2•TCF7L2•wild homozigot CC•Polimorfisme•CT •TT rs7903146 -puternic asociat cu diabet de tip 2



important in protecting the cell environment from internally generated oxidative free radicals, especially those generated during energy production. It binds to the superoxide by-products of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen.



Glutathione peroxidase is a “selenoprotein”, i.e. dependent on selenium for its activity. Gpx1 is an anti-oxidant enzyme that protects the cell by removing hydrogen and lipid peroxides.



Catalase is an endogenous antioxidant enzyme that neutralizes hydrogen peroxide H2O2 (produced by manganese superoxide dismutase, SOD2) into H2O and O2. The enzyme works together with superoxide dismutase and glutathione peroxidase as a primary defence against oxidative stress.



Microsomal epoxide hydrolase is a detoxification enzyme that catalyzes the hydrolysis of epoxides, which can be mutagenic, to less reactive, more water-soluble products which can be excreted from the body. It plays an important role in both the activation and detoxification of exogenous chemicals such as polycyclic aromatic hydrocarbons (PAHs, e.g. carcinogens found in cigarette smoke and grilled meat).



Interleukin-6 (IL-6) is a pro-inflammatory cytokine that increases the level of inflammation throughout the body – it is secreted by T-cells and macrophages, stimulating the immune response to various insults such as trauma (e.g. burns and other tissue damage that causes inflammation). It is also involved in the response to bacterial infections.



Tumour necrosis factor (TNF) is a cytokine involved in systemic inflammation – it promotes the inflammatory response (e.g. causing many of the problems associated with autoimmune diseases and as such is a pharmaceutical target in diseases such as rheumatoid arthritis.



Apolipoprotein C-III is expressed in the liver and intestine and is found primarily in LDL- and VLDL- cholesterol particles. It inhibits the activity of lipoprotein lipase, delaying clearance of triglyceride- rich lipoproteins from the blood.



LPL variants often result in hypertriglyceridemia, lower HDL-cholesterol levels, and elevated risk of heart and cerebrovascular disease. The 1595 C>G common variant, however, has the opposite effect.



MTHFR is a key protein in the metabolism of folic acid (a B vitamin) which is involved in DNA synthesis and DNA methlyation pathways. The latter pathway consumes homocysteine and maintains normal levels of this cardiovascular disease risk factor.



The SNP results in an amino acid change from methionine (Met) to threonine (Thr). The Thr (C) allele is associated with higher plasma angiotensinogen levels which are related to salt dependent hypertension – i.e. when dietary salt is high there is increased risk of high blood pressure.



The D allele is associated with fatness and increased cardiovascular risk as well as negative effects on insulin sensitivity. The ACE I allele on the other hand is linked to salt sensitive hypertension. There are also reported effects of both alleles on physical activity



PPARG gene contains a so-called “gain of function” polymorphism (i.e. it can have positive effects) which changes the amino acid at position 12 from Proline to Alanine – this version, Ala, which is thought to reduce PPARG production, is associated with a decreased risk of insulin resistance and type 2 diabetes although it depends on environmental factors, especially diet and weight.



Glutathione-S-transferase M1is a member of the family of sulfotransferases involved in the metabolism of toxins, such as xenobiotics, carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, during the 2-phase detoxification reaction carried out primarily by the liver.



Glutathione-S-transferase T1 is a member of the family of sulfotransferases involved in the metabolism of toxins, such as xenobiotics, carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, during the 2-phase detoxification reaction carried out primarily by the liver.



The VDR gene is expressed in most tissues of the body and has diverse effects on different systems. One role is in the regulation of the intestinal transport of calcium, others include though regulating a variety of other metabolic pathways, such as those involved in the immune response and cancer.



The T version is associated with lower bone mineral density and increased incidence of osteoporotic fracture. The SNP affects the ratio of collagen alpha-1 to collagen alpha-2 in type 1 collagen by leading to increased production of the alpha-1 polypeptide relative to alpha-2.













Testul GenoMav full nutrition

Obesity

Stress oxidative

Detoxification

Inflammation

Metabolism of vitamins, salt, lipids, caffeine

Bone health


«Nutrigenetic Testing »





Results and Biological processes

«Nutrigenetic Testing » BMI - easy to understand graphic and suggestions….



LCT gene Lactose is digested by the enzyme lactase.

In many regions of the world its presence decreases significantly with age, so digesting lactose becomes difficult.

Polymorphism C / C means that the person does not possess genetic variant that allows durability lactase therefore will have insufficient capacity to digest lactose.Dr. Maria Vranceanu, Nutritionist , Biologist, Ketogenic Diet & Nutrigenetics Specialist

In Europe, this genetic variation determines the persistence of lactase which enables digest lactose in all stages of life.


BMI - easy to understand grafic and suggestions….



PPARG gene and ACE genePPARG gene encoding is a transcription factor that influences the glucose levels and insulin levels.

Due to the presence or absence of polymorphism allele Pro12 Ala influence gene expression, and therefore, the amount of protein produced.

It was shown that heterozygous individuals for alleles Ala have beneficial effects on blood glucose levels and insulin.

In the case of a genotype Pro homozygous alleles for genotype I / I ACE gene it is recommended reducing consumption of refined carbohydrates and sugars, eating foods with low GI (whole grains), with the glycemic load not to exceed 80 grams per day .


Diet prescription Refined carbohydrate diet = reduction and glycemic load (GL) <80 g / day.


APOC3 gene and gene LPL Recent studies have shown an interaction between these two genes and nutrition. Apolipoprotein C3 is a very low density lipoprotein a (VLDL) and consists mainly of triglycerides. It inhibits lipoprotein lipase APOC3 (LPL) and slows catabolism of triglycerides.

Genotype G / G APOC3 is associated with elevated levels of TG. The resulting LPL gene (CC) contributes to changing the lipid profile and is associated with low levels of HDL (good) cholesterol and high levels of triglycerides.


Diet prescription = reducing dietary saturated fat below 16 grams per day, eliminating trans fats, substituting them with a greater amount of olive oil


5. CYP1A2 * 1F gene = 5 CYP1A2 is the gene coding for the cytochrome P450 enzyme involved in phase I (activation) the elimination of toxins - such as carcinogens of meat and smoke - and caffeine metabolism . The genotype of the homozygous alleles A (AA) coding for the enzyme activity rapidly and therefore would be activated quickly prepared meat potentially toxic substances at high temperatures.


Diet perscription = drastic reduction in the consumption of grilled meats and smoked maximum once a week. As for caffeine, this form of the enzyme metabolizes well.


GSTM1 Gene GSTM1 is the gene coding for the enzyme glutathione S-transferase family of detoxifying isozymes , which catalyze the conjugation different toxic molecules with glutathione in order to make them less reactive and easily removed from the body.

GSTM1 gene polymorphism type insertion / deletion, I / D, causes loss of enzymatic functionality.

Diet prescription = Increased consumption of cruciferous diet



SOD2 gene SOD2 is the gene coding for the enzyme manganese superoxide dismutase MnSOD. Located in the mitochondrial matrix , and is the first line of defense of cells against free radicals (ROS).

MnSOD catalyzes dismutases of superoxide into oxygen and hydrogen peroxide, thereby removing free radicals from source.

Free radicals, although evolutionary were appointed to assist in the maintenance of cellular homeostasis are toxic molecules able to induce oxidative damage to biological macromolecules indiscriminately, and are primarily responsible for certain pathological conditions and aging. The genetic test demonstrated heterozygosity for this enzyme.

Profile C / T is associated with an intermediate enzyme activity.

Diet prescription = increase daily intake of folic acid and vitamins B6 and B12.



gene IL6 and TNF gene IL6 and genaTNF are gene, coding for pro-inflammatory cytokines homonyms and are involved in the regulation of immune response.

Polymorphisms present in these genes, IL-6-174G / C and TNF-308G / A, affect the amount of cytokines produced.

Polymorphism in the gene IL-6, GC, is the substitution of a G (guanine) and C (cytosine), lead to a tendency of the increase in the synthesis of the cytokines same name , guanine, cytosine

Diet perscription = increasing the amount of omega 3



8. MTHFR gene MTHRF is the gene coding for the enzyme that is involved in the metabolism and use of folic acid and vitamins B6 and B12.

This enzyme plays a central role in DNA synthesis and methylation.

The genotype of 677C / T codes for an for less efficient enzyme associated wit h increased plasma levels of homocysteine.

Diet prescription = increase daily intake of folic acid and vitamins B6 and B12.Dr. Maria Vranceanu, Nutritionist , Biologist, Ketogenic Diet & Nutrigenetics Specialist


VDR gene = VDR gene is coding for the vitamin D receptor which affects the production of various proteins, some of which are involved in the use of calcium. The genotype heterozygous for the allele C (CT), has been shown to influence the absorption of calcium and the bone structure.

Diet prescription= increasing amounts of vitamin D and calcium.



ACE geneACE gene, which is coding for the homonymous enzyme ACE that plays a key role in cardiovascular homeostasis.

Gene polymorphism is present in type insertion / deletion (allelesI-insertion-deletion allele D) and which affects the enzymatic activity.

Recent studies have highlighted the link between genotype I / I, I / D and sensitivity to salt. Test further showed that genotype I / I are predisposed to hypertension when salt intake is excessive.

It is recommended to not consume more than 5.5 grams of salt per day, which corresponds to 2.2 grams of Na, the molecule responsible for the taste of salt, and salt’s effects on blood pressure.

Diet prescription = reducing salt intake.



ADH1C gene Achohol dehydrogenase 1C metabolizes to form acetaldehyde, the toxic compound responsible for the negative effects of excessive consumption.

In turn, acetaldehyde is metabolized by the enzyme aldehyde dehydrogenase in non-toxic compounds.

The gene variant tested produce changes in amino acid sequence which modifies enzyme efficiency.

For example, in the case of the homozygous genotype A / A alleles Ile (Ile-Ile), which his characterized by the presence of isoleucine in a specific position of the sequence amino acid, enzyme catalytic efficiency is elevated metabolizing alcohol more quickly than Val genotype.

Diet prescription = reduce the amount of alcohol.





Personalized RDATrue Nutritional Prescription



Carb SensitivitySaturated Fat Sensitivity Exercise Level









Questions?

Maria Vranceanu,Nutritionist , Biologist, Ketogenic Diet & Nutrigenetics Specialist marievranceanu.com


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The Secret to Long Life is Personalized Nutrition - Nutrigenetic Testing and your health