Genetické vlivy na hladiny vitamínu E

ApoE

ApoE 3 - ‘neutral’ genotype

• (Cys112, Arg158)
• Most common isoform in 40–90% of the population [8]

ApoE-2 - protective

• (Cys112, Cys158)
• Receptor-binding region is inactivated
• Delayed clearance of hepatic and intestinal remnant lipoproteins
• Hyperlipoproteinemia
• Associated with a mild form of atherosclerosis progression [8]
• Lowest plasma VE concentrations were found in Apo-2/2

ApoE-4 - risky

• (Arg112, Arg158)
• Consequences in the structure and function of Apo-E
• Modulating the prognosis and progression of cardiovascular disease
• Reshapes the lipid-binding site
• Targets large triglyceride-rich VLDL rather than small phospholipid-rich HDL
• Higher levels of LDL cholesterol
• Favors the induction of atherosclerotic lesions [8].
• 42% higher risk of cardiovascular disease than carriers of the ApoE-3/3 genotype
• Greater risk of Alzheimer’s disease
• Negatively associated with longevity [8]
• May be expected to influence VE status
• Presence of the e4 allele was accompanied by the highest plasma levels
• Range of 14.2 µmol/L was observed between E2/E2 and E4/E2 genetic groups [8]
• Higher VE tissue levels observed with the Apo-E4 genotype may be due to different reasons
• Decreased catabolism of LDL and VE retention
• Decreased expression of lipoprotein receptors
• Delay the cellular uptake of vitamin E in Apo-E4 carriers
• Activated intracellular degradation of tocopherols in the Apo-E4 genotype
• Contributing to lower VE in peripheral tissues
• Lower levels of SR-B1 accompanying impaired cellular VE delivery through this [8]
• ApoE-E4 carriers might have an increased demand for VE in order to counteract
• Reduced uptake into extrahepatic tissues
• Higher degradation rate [8]
• Genetic variants may contribute to exacerbate the impact of ApoE alleles
• Rs449647 (491A>T) in the promoter of the gene
• Results in 63% decrease in its activity [8]

Association between genetic variants and response to long-term vitamin E supplementation

ATBC Study

• Randomized, placebo-controlled, double-blind intervention trial of alpha-tocopherol and ß-carotene supplementation that initially focused on the prevention of lung and other cancers [5]
• Genome-wide association study (GWAS)
• Common variants
• Circulating alpha-tocopherol concentrations
• Following 3 y of controlled supplementation
• 2112 middle-aged,
• Male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort
• Alpha-tocopherol (50 mg/d)
• Fasting serum alpha-tocopherol concentrations measured after 3 y
• Models adjusted for age, BMI, serum total cholesterol, and cancer case status [5]

rs964184 on 11q23.3 (P = 2.6 × 10-12)

• (11q23.3:116648917, hg19, P = 2.6 × 10-12)
• Rs964184 in BUD13/ZNF259/APOA5
• Located between the BUD13 homolog (Saccharomyces cerevisiae) and zinc finger protein 259 (ZNF259) and only 359 bp 3' to ZNF259 [5]
• Subgroup analysis of men whose baseline concentrations of serum alpha-tocopherol were above the median value of 11.5 mg/L (26.7 µmol/L)
• Confirmed association of rs964184 with the 3-y supplemented ?-tocopherol concentrations (P = 4.8 × 10-10, ß = 0.08) [5]
• Minor allele in the same SNP, rs964184 associated with
• Lower HDL cholesterol
• Higher TG concentrations according to the results of recent meta-analyses [5]
• Associated with unsupplemented serum alpha-tocopherol in a population of women primarily comprosed of individuals who never smoked [5]

rs2108622 on 19pter-p13.11 (P = 2.2 × 10-7)

• Located between LOC100128347 and BUD13. [5]
• (19p13.12:15990431, hg19, P = 2.2 × 10-7)
• Is a missense mutation [V(Val) to M (Met)] in the region of CYP4F2 (cytochrome P450, family 4, subfamily F, polypeptide 2) [5]
• Associated with unsupplemented serum alpha-tocopherol in a population of women primarily comprosed of individuals who never smoked [5]

rs7834588 on 8q12.3 (P = 6.2 × 10-7)

• (8q12.3:63883593, hg19, P = 6.2 × 10-7)
• In an intron of Na+/K+ Transporting ATPase Interacting Protein 3 (NKAIN3) [5]

Výsledky

• Combined, these SNP explain 3.4% of the residual variance in serum alpha-tocopherol concentrations during controlled vitamin E supplementation - standard 50-mg daily dose [5]
• The mean serum concentration of alpha-tocopherol after 3 y of the standard dose-trial supplementation was higher than the baseline concentrations
• 18.1 vs. 11.9 mg/L (42.0 vs. 27.6 µmol/L) (P < 0.001)
• Wide range of response to 50 mg/d vitamin E supplementation
• Highly significant (P < 0.001) based on paired comparisons [mean change, 6.2 mg/L (14.4 µmol/L)]
• No significant changes between baseline and 3-y serum total and non-HDL cholesterol concentrations

c.205-1G>T

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

c.400C>T

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• [El Euch-Fayache et al 2014] [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

c.486delT

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• Before age ten years, homozygoté [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

c.513_514insTT

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• Before age ten years, homozygoté [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

c.530-531AG>GTAAGT

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• Before age ten years, homozygoté [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

c.552+2T>A

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

c.744delA

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

• Mediterranean or North African ancestry [4]
• 132 Tunisian individuals with AVED, 91.7% were homozygous for the c.744delA pathogenic variant;
• 8.3% of individuals were homozygous for other pathogenic variants
• Most individuals are homozygous or compound heterozygous for one of the known pathogenic variants. [4]
• Associated with early onset
• A severe course
• Slightly increased risk for cardiomyopathy
• Mainly observed in individuals of Mediterranean or North African descent
• Severity may vary considerably even in persons from the same family
• Onset of symptoms may vary between ages 3 and 12 years [Cavalier et al 1998, Marzouki et al 2005]. [4]

p.Ala120Thr

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• After age ten years [4] [Cavalier et al 1998]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

p.Arg134Ter

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• Before age ten years, homozygoté [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

p.Arg221Trp

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• After age ten years [4] [Cavalier et al 1998]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

p.Arg59Trp

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]

• Before age ten years, homozygoté [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

p.Glu141Lys

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• Before age ten years, homozygoté [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

p.His101Gln

• Patogenická mutace alpha-TTPA spojené se symptomy z deficitu vit. E [4]
• Nearly complete penetrance in individuals who are homozygous or compound heterozygous for a TTPA pathogenic variant. [4]
• Carrier (Heterozygote) requires prior identification of the TTPA pathogenic variants in the family.
• Moderately lowered plasma vitamin E concentration in heterozygotes is not a sensitive enough measure to distinguish between heterozygous carriers and non-carriers. [4]

• Associated with late-onset disease (age >30 years)
• A mild course,
• Increased risk for pigmentary retinopathy
• Primarily reported in individuals of Japanese descent. [4]
• TTPA pathogenic variant in 21 of 801 randomly selected inhabitants of a Japanese island [4]
• One individual had previously been diagnosed with AVED [4]
• Calculated prevalence of one homozygous individual per 1500 inhabitants [4]
• Pathogenic variant was not detected in 150 unrelated individuals from Tokyo [4]

rs1031551

• In alpha-TTP
• Was associated with a high level of significance [5]
• P = 2.9 × 10-5 in TTPA [5]

rs1042031

T allele

• Associated with higher plasma alpha-tocopherol in chylomicrons after the consumption of VE-rich meal food [8]

rs11057830

• In scavenger receptor class B member 1 (SCARB1) on 12p24.31
• Highly significantly related to the baseline unsupplemented alpha-tocopherol concentrations (P = 2.0 × 10-8)
• Weakly associated with circulating alpha-tocopherol after supplementation and unrelated to change in alpha-tocopherol concentrations [5]
• Intron region of SCARB1 gene
• Related to lower plasma alpha-tocopherol in a genome-wide association study
• Further confirmed in the analysis of a supplementation trial [8]
• Lower expression or functionality of SR-B1 - disturbances in lipid metabolism
• Including postprandial triglyceride response
• Handling of lipoproteins
• Can be worsened in the case of obesity, particularly if lower levels of plasma VE are found [8]

rs11789603, rs2274873, rs4149314, and rs4149297

• Variants located near the ABCA1 gene
• Lower transcription rate, and/or lower transporter concentrations
• Associated with lower VE levels after an alpha-tocopherol rich meal [8]
• No information regarding cholesterol transport and lipoprotein metabolism has been addressed in parallel
• Remains inconclusive whether VE supplementation would be a reliable strategy [8]
• Riziko suprese ABCA1 genu vyšší dávkou vit. E - assoc. s vyšší KV zvířat

rs1205682

• 1753C/T
• In the promoter of alphaTTP
• Related with higher transcriptional rates alpha-TTP [8]

rs1467568

• A/G
• Sirtuin 1

minor alleles(G)

• Protective proti obezitě [8]
• Elevated risk to having a greater BMI was related to a higher copy number of the most common haplotype among subjects with low VE intake [8]
• V.s. capacity of VE to modify the association between SIRT1 variants and obesity [8]

rs1527479

• In CD36
• In high linkage disequilibrium vith alpha-tocopherol levels [8]

rs1695

• In glutathione S-transferase gene (GSTP1)
• Alpha-tocopherol supplementation in healthy individuals influences the production of inflammatory cytokines in a genotype-dependent manner
• Influences IL-6

rs1713222

G allele

• Associated with higher plasma alpha-tocopherol in chylomicrons after the consumption of VE-rich meal food [8]

rs1761667

• Polymorphism located in the intron region of the CD36 gene
• Most of the CD36 polymorphisms are not strongly associated with obesity
• Contribute to interindividual variability in plasma lipid and lipoprotein profiles
• Influencing cardiovascular risk [8]

A allele

• Associated with a reduced expression of the CD36 transcript
• Reduced total and surface protein in monocytes compared with allele G
• Reduced sensitivity to fatty taste
• Increased perception of creaminess
• Greater preference for fats added to foods [8]
• Appear to promote a protective profile concerning circulating lipoproteins [8]
• Lower CD36 expression seems to be metabolically protective

Homozygotes G

• Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study identified
• Homozygous individuals for the G allele had
• lower plasma alpha-tocopherol concentration (3%)
• Did not attain statistical significance when corrected for multiple testing [8]
• Promotion of high VE intake in appropriate subjects may be a dietary strategy to counteract excess CD36 protein [8]

rs1800629

• 308G>A polymorphism in the TNFalpha gene

A allele

• Associated with the increased production of TNFalpha
• This expression is modulated by VE status

A/G or A/A

• Immunity cells from healthy individuals, isolated after one year of oral alpha-tocopherol supplementation (182 mg/day)
• Stimulated with lipopolysaccharide (LPS)
• Produced lower levels of TNFalpha in response to LPS
• Suggesting that the anti-inflammatory effect of VE is specifically targeted in those individuals who are genetically predisposed to show higher inflammation [8]

rs1800896

• Located in IL10 gene promoter
• Modulates the production of IL-1beta.

rs1805081

• His215Arg in Niemann–Pick disease type C1 (NPC1) protein
• Genome Wide Association (GWA) study
• Non-synonymous variant
• Early-onset and morbid adult obesity in the European population [8]
• Involvement of common genetic variants in adult-onset obesity, body fat mass, and type 2 diabetes [8]

rs2108622 - V433M

• G to A nucleotide change at mRNA position 1347 in CYP4F2
• Leading to a valine to methionine substitution at amino acid position 433
• V433M polymorphism has been associated with
• Altered warfarin dose requirements in humans
• Hypertension
• Ischemic stroke in several populations [9]
• Speculative mechanisms behind these associations relate to the
• Role of CYP4F2 in 20-hydroxyeicosatetraenoic acid (20-HETE) production [9]
• Putative role of CYP4F2 as a phylloquinone oxidase [9]
• V433M substitution in CYP4F2 results
• In decreased omega-hydroxylation of AA [9]
• Těžko interpretovat význam laboratorního nálezu
• Redundancy in arachidonate 20-hydroxylase activity among multiple CYP450 enzymes and the potential for compensatory degradation of 20-HETE [9]
• Lower specific activity toward the TOH
• But was without significant effect with the T3 substrates [9]
• May have increased plasma and tissue levels of TOH
• More pronounced response to TOH supplementation than individuals carrying wild-type alleles [9]

Minor allele

• Frequency of 17 and 9% in the European American and African American populations examined [9]
• Frequency for V433M variant 26% in combined Asian sampling panel (Chinese and Japanese HapMap dataset) [9]

Rs2108622

• CYP4F2 variant
• Associated with increased serum alpha-tocopherol in subjects from the ATBC trial
• This variant has reduced omega-hydroxylation activity (Major et al., 2012).
• G to A nucleotide exchange
• Causing the substitution of avaline for methionine (V433M)
• Associated with decreased baseline alpha-tocopherol levels [8]
• Related with decreased enzymatic activity for tocopherols
• But does not affect the hydroxylation of tocotrienols [8]
• Might explain inconsistent findings after supplementation trials
• CYP4F2 possibly playing a moderate role in affecting the pharmacokinetics of VE [8]

rs2301241

• 793T > C
• Promoter of the gene coding for Thioredoxin (TXN)
• Related to oxidative stress [8],
• Enzymes involved in the detoxification pathway are also relevant in the action of VE
• Polymorphisms in TXN may affect adiposity, depending on VE status

genotype T/T

• In gene TXN
• Larger waist circumference in conjunction with low dietary intake of VE (pod 9 mg/day)

rs3093105 - W12G

• T to G nucleotide change at mRNA position 84 in CYP4F2
• Leading to a tryptophan to glycine substitution at amino acid position 12 [9]

• W12G variant
• Trend toward higher specific activity accompanying the W12G substitution [9]
• Had significantly greater omega-hydroxylase specific activity toward the 3 TOH tested and all 3 T3 [9]
• May have lower plasma and tissue concentrations of TOH [9]
• May have little or no change in response to TOH or T3 supplementation [9]

Minor allele

• Frequency of 11 and 21% in the European American and African American populations examined [9]
• Frequency for W12G variant 6 % (?) [9] combined Asian sampling panel (Chinese and Japanese HapMap dataset) [9]

rs3093105

• SNPs in CYP4F2
• Functional changes in the enzymatic activity of the cytochrome
• T to G nucleotide exchange
• Leading to a tryptophan to glycine substitution at amino acid position 12 (W12G)
• Showing increased enzymatic activity in hydroxylating both tocopherols and tocotrienols [8]

rs3135506

• Exchange of a serine for a tryptophan (S19W or 56C>G) in APO AV

G allele

• Very rare worldwide
• Associated with a great prevalence for metabolic syndrome
• Accompanied by a higher prevalence of plasma hypertriglyceridemia [8]
• Greater alpha-tocopherol [8]

rs34358293

• 945A/G
• Repression of the promotor activity of alpha-TTP [8]

rs361525

• TNFalpha 238G/A

Rare allele (A)

• Decreased production of TNFalpha
• Did not reproduce the effects observed for rs1800629 ::8]

rs4135168

Carriers of allele G

• In gene TXN
• Larger waist circumference in conjunction with low dietary intake of VE (pod 9 mg/day)

rs4149268, rs3890182, and rs1883025

• Variants located near the ABCA1 gene
• Associated with HDL concentrations in different studies [8]
• Although no gene–vitamin E significant interaction with HDL levels has been found [8]

rs4238001

• Missense variant Gly2Ser

Minor allele (T)

• Associated with lower HDL-cholesterol and LDL-cholesterol in type 2 diabetics in the Framingham Heart Study [8]
• Higher SR-B1 degradation and lower protein levels [8]
• Meta-analysis across large race and ethnic population groups associated with greater risk of coronary heart disease [8]

rs4643493

T allele

• Associated with higher plasma alpha-tocopherol in chylomicrons after the consumption of VE-rich meal food [8]

rs497849

Alela G

• Elevated risk to having a greater BMI was related to a higher copy number of the most common haplotype among subjects with low VE intake [8]
• V.s. capacity of VE to modify the association between SIRT1 variants and obesity [8]

rs5082

T/T genotype Apo-AII

• Associated with postprandial hypertriglyceridemia response
• Greater cardiovascular risk compared with individuals carrying C/T or C/C allele combinations [8]

rs5888 - A350A

• Exon 8 of Scavenger receptor class B type 1 gene (SCARB1)

Minor variant (C) for T

• Related to splicing activity
• Dyslipidemia, coronary heart disease, and related in gender and age-dependent manner
• No conclusive data regarding its precise role [8]

CT carriers

• Associated with an atherosclerosis-protective effect in a Lithuania population-based study [8]
• Increased risk of age-related macular degeneration in French and North American populations
• Potential impaired function of SR-B1 as a transporter of functional lipophilic compounds such as cholesterol, lutein, and VE [8]
• Poor bioavailability of antioxidants in particularly dependent tissues
• More prone to showing a pro-inflammatory profile or a deficit in redox homeostasis

TT carriers

• Had lower alpha-tocopherol levels in plasma than CC and CT carriers ( male subjects), with the latter having higher levels (+16.4% more than TT) [8]

rs6472071

• 1410A/T
• In the promoter of alphaTTP
• Related with higher transcriptional rates alpha-TTP [8]

rs6472073

• In alpha-TTP
• Was associated with a high level of significance [5]
• P = 2.1 × 10-5

rs662799

• 1131T>C in APO AV

Minor variant (C)

• Associated with lower Apo-AV plasma concentration
• Correlates with dyslipidemia
• Carriers show remodeling of the lipoprotein profile toward atherogenic dyslipidemia
• Large VLDL
• Small LDL and HDL [8]
• Potential modulation of VE by APOA5 in diabetic patients carrying the C variant of rs662799, higher plasma triglycerides are shown in combination with higher plasma VE
• Not associated with improved antioxidant parameters [8]
• Similar results have been found in healthy school children [8]

rs670

A allele

• Associated with an in vitro higher gene transcription rate of Apo-AI
• Higher levels of HDLc
• Higher Apo-AI in plasma [8::
• Associated with higher levels of HDL
• Lower risks of visceral obesity, diabetes, and hypertriglyceridemia [8]

rs693

minor allele (T) ABO B

• Associated with a greater risk of elevated
• Total cholesterol [8]
• LDL-cholesterol levels in blood [8]
• Strong influence of this variant on the risk of dyslipidemia
• Lifestyle intervention based on calorie restriction and physical activity proved to be useful for the carriers of the most frequent allele of rs693
• But not for carriers of the minor allele, in an attempt to improve cholesterol profile [8]
• Interaction between rs693 with serum LDL cholesterol and VE has been reported in non-Hispanic whites and Mexican-American populations
• Heterogeneous response to VE bioavailability
• Estimated coefficient of variation of 81%

rs6994076

• 980A/T
• Repression of the promotor activity of alpha-TTP [8]

T/T genotype of the 980A/T polymorphism

• Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) intervention study
• Associated with approximately 3% lower serum levels of alphatocopherol at baseline in comparison with the other genotypes
• Lower response (25%) to VE supplementation was observed in serum alpha-tocopherol concentration in T/T subjects
• In comparison with those carrying two copies of the common allele [8]

rs73684515

• 439A/G
• Repression of the promotor activity of alpha-TTP [8]
• These SNPs might influence the balance of alpha-tocopherol between liver and tissues

rs740603

• Catechol-O-methyltransferase (COMT) gene

G/G carriers

• Larger waist circumference in conjunction with low dietary intake of VE (pod 9 mg/day)
• In comparison with other genotypes [8]
• Relationships are not sustained among subjects that regularly have higher intakes of VE (nad 9 mg/day) [8]

rs74684018

• 344C/T
• In the promoter of alphaTTP
• Related with higher transcriptional rates alpha-TTP [8]

rs7895833

• Sirtuin 1

minor alleles(G)

• Protective proti obezitě [8]

alleles A

• Elevated risk to having a greater BMI was related to a higher copy number of the most common haplotype among subjects with low VE intake [8]
• V.s. capacity of VE to modify the association between SIRT1 variants and obesity [8]

rs80169698

• 675G/A
• Repression of the promotor activity of alpha-TTP [8]