Genetic variation in alcohol dehydrogenase 1C and the beneficial effect of alcohol intake on coronary heart disease risk in the Second Northwick Park Heart Study

Younis, Jenan; Cooper, Jackie A.; Miller, George; Humphries, Steve E.; Talmud, Philippa J.

doi:10.1016/j.atherosclerosis.2004.12.010

Cited by 47 publications

(35 citation statements)

References 26 publications

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“…Another study also found a significant interaction (Pϭ0.02) between alcohol intake and the ADH1C genotype, but only after performing post hoc regrouping of the alcohol categories, and in contrast to the previous report, 17 the lower risk was found among individuals with the lowest alcohol intake (0.7 to 2 drinks/wk). 18 In yet other studies, there was no significant interaction between alcohol intake and the ADH1C genotype (Table 4). 19 -21 Finally, our study which is the largest so far could not confirm either of the previous findings; our post hoc power calculations showed that we had 97% power to pick up a ADH1C-alcohol interaction of a size similar to what was found in the Hines study.…”

Section: Discussionmentioning

confidence: 73%

“…In the first study on the subject, which was conducted among American physicians, ADH1C slow metabolizers seemingly had a lower risk of myocardial infarction (MI) than ADH1C fast metabolizers, but this was confined to individuals in the highest drinking category 17 ; however, this is in contrast to findings from another study, where this effect was only observed in men with a very low intake (less than 3 drinks per week). 18 In some other studies, no significant interaction between the ADH1C genotype and alcohol on risk of coronary heart disease was found. 19 -21 The potential interaction between ADH1B genotypes and alcohol has not been addressed among whites, most likely because the ADH1B ⅐ 2 allele is relatively rare in this population.…”

Section: Clinical Perspective On P 514mentioning

confidence: 88%

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Alcohol Intake, Myocardial Infarction, Biochemical Risk Factors, and Alcohol Dehydrogenase Genotypes

Tolstrup

Grønbæk

Nordestgaard

2009

Circ Cardiovasc Genet

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Background-The risk of myocardial infarction is lower among light-to-moderate alcohol drinkers compared with abstainers. We tested associations between alcohol intake and risk of myocardial infarction and risk factors and whether these associations are modified by variations in alcohol dehydrogenases. Methods and Results-We used information on 9584 men and women from the Danish general population in the Copenhagen City Heart Study. During follow-up, from 1991 to 2007, 663 incident cases of myocardial infarction occurred. We observed that increasing alcohol intake was associated with decreasing risk of myocardial infarction, decreasing low-density lipoprotein cholesterol and fibrinogen, increasing diastolic and systolic blood pressure and high-density lipoprotein cholesterol, and with U-shaped nonfasting triglycerides. In contrast, ADH1B and ADH1C genotypes were not associated with risk of myocardial infarction or with any of the cardiovascular biochemical risk factors, and there was no indication that associations between alcohol intake and myocardial infarction and between alcohol intake and risk factors were modified by genotypes. Conclusions-Increasing alcohol intake is associated with decreasing risk of myocardial infarction, decreasing low-density lipoprotein cholesterol and fibrinogen, increasing diastolic and systolic blood pressure and high-density lipoprotein cholesterol, and U-shaped nonfasting triglycerides. These associations were not modified by ADH1B and ADH1C are genotypes. (Circ Cardiovasc Genet. 2009;2:507-514.)

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Section: Discussionmentioning

confidence: 73%

Section: Clinical Perspective On P 514mentioning

confidence: 88%

Alcohol Intake, Myocardial Infarction, Biochemical Risk Factors, and Alcohol Dehydrogenase Genotypes

Tolstrup

Grønbæk

Nordestgaard

2009

Circ Cardiovasc Genet

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“…27 Genetic variants at this locus have also been identified that interact with alcohol consumption to increase heart disease. 28,29 However, this finding has not been observed in all studies. 30 We observed that 3 SNPs in 2 lipid metabolism genes were associated with the levels of Apo B/A1 ratio and with acute MI.…”

Section: Discussionmentioning

confidence: 74%

Genetic Variants Associated With Myocardial Infarction Risk Factors in Over 8000 Individuals From Five Ethnic Groups

Anand

Xie

Paré

et al. 2009

Circ Cardiovasc Genet

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Background-Myocardial infarction (MI) is a leading cause of death globally, but specific genetic variants that influence MI and MI risk factors have not been assessed on a global basis. Methods and Results-We included 8795 individuals of European, South Asian, Arab, Iranian, and Nepalese origin from the INTERHEART case-control study that genotyped 1536 single-nucleotide polymorphisms (SNPs) from 103 genes. One hundred and two SNPs were nominally associated with MI, but the statistical significance did not remain after adjustment for multiple testing. A subset of 940 SNPs from 69 genes were tested against MI risk factors. One hundred and sixty-three SNPs were nominally associated with a MI risk factor and 13 remained significant after adjusting for multiple testing. Of these 13, 11 were associated with apolipoprotein (Apo) B/A1 levels: 8 SNPs from 3 genes were associated with Apo B, and 3 cholesteryl ester transfer protein SNPs were associated with Apo A1. Seven of 8 of the SNPs associated with Apo B levels were nominally associated with MI (PϽ0.05), whereas none of the 3 cholesteryl ester transfer protein SNPs were associated with MI (PՆ0.17). Of the 3 SNPs most significantly associated with MI, rs7412, which defines the Apo E2 isoform, was associated with both a lower Apo B/A1 ratio (Pϭ1.0ϫ10

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“…Thus, this polymorphism could modify the association of alcohol consumption with disease risk but with an effect anticipated only among drinkers. Indeed, such an interaction between alcohol consumption and ADH1C genotype has been observed in some, but not all (8,12), studies of coronary heart disease and levels of HDL cholesterol (13)(14)(15).…”

mentioning

confidence: 96%

Alcohol Consumption and Type 2 Diabetes

et al. 2007

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OBJECTIVE-We sought to investigate whether a polymorphism in the alcohol dehydrogenase 1c (ADH1C) gene modifies the association between alcohol consumption and type 2 diabetes.RESEARCH DESIGN AND METHODS-In nested case-control studies of 640 women with incident diabetes and 1,000 control subjects from the Nurses' Health Study and 383 men with incident diabetes and 382 control subjects from the Health Professionals Follow-Up Study, we determined associations between the ADH1C polymorphism, alcohol consumption, and diabetes risk.RESULTS-Moderate to heavy alcohol consumption (Ͼ5 g/day for women and Ͼ10 g/day for men) was associated with a decreased risk of diabetes among women (odds ratio [OR] 0.45 [95% CI 0.33-0.63]) but not men (1.08 [0.67-1.75]). ADH1C genotype modified the relation between alcohol consumption and diabetes for women (P interaction ϭ 0.02). The number of ADH1C*2 alleles, related to a slower rate of ethanol oxidation, attenuated the lower risk of diabetes among women consuming Ն5 g alcohol/day (P trend ϭ 0.002). These results were not significant among men. Results were similar in pooled analyses (P interaction ϭ 0.02) with ORs for diabetes among moderate drinkers of 0.44 (95% CI 0.21-0.94) in ADH1C*1 homozygotes, 0.65 (0.39 -1.06) for heterozygotes, and 0.78 (0.50 -1.22) for ADH1C*2 homozygotes compared with those for ADH1C*1 homozygote abstainers (P trend ϭ 0.02). CONCLUSIONS-ADH1C genotype modifies the associationbetween alcohol consumption and diabetes. The ADH1C*2 allele, related to a slower oxidation rate, attenuates the lower diabetes risk among moderate to heavy drinkers. This suggests that the association between alcohol consumption and diabetes may be causal but mediated by downstream metabolites such as acetate rather than ethanol itself. Diabetes

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Genetic variation in alcohol dehydrogenase 1C and the beneficial effect of alcohol intake on coronary heart disease risk in the Second Northwick Park Heart Study

Cited by 47 publications

References 26 publications

Alcohol Intake, Myocardial Infarction, Biochemical Risk Factors, and Alcohol Dehydrogenase Genotypes

Alcohol Intake, Myocardial Infarction, Biochemical Risk Factors, and Alcohol Dehydrogenase Genotypes

Genetic Variants Associated With Myocardial Infarction Risk Factors in Over 8000 Individuals From Five Ethnic Groups

Alcohol Consumption and Type 2 Diabetes

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