title: 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.
abstract: Alcohol dehydrogenase 1C (ADH1C or ADH3) genotype reportedly modifies the association between alcohol consumption and coronary heart disease (CHD) risk, as well as influencing plasma high-density lipoprotein (HDL) levels [Hines LM, Stampfer MJ, Ma J, et al. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med 2001;344:549-55]. This relationship has been examined in a sample of middle-aged (50-61 years) men (total of 2773 with 220 CHD events), participating in the prospective Second Northwick Park Heart Study (NPHS II). Alcohol consumption was assessed by questionnaire as the number of units consumed in the previous week. Drinkers experienced lower CHD risk than abstainers [hazard ratio (HR) 0.73 (95% confidence intervals (CI) 0.53, 0.99; p=0.04)] and had significantly higher HDL and apolipoprotein (apo)AI concentrations (both p<0.0001) and a lower fibrinogen (p=0.02). Overall, there was no effect of ADHC1 gamma1>gamma2 genotype on plasma levels of HDL, apoAI or fibrinogen or on CHD risk. To consider whether the effect of alcohol consumption on risk was modulated by genotype, the men were divided into abstainers, modest drinkers (1-3 units/week) and those who consumed more than 3 units/week. Significant alcohol:genotype interaction on CHD risk was observed (p=0.02), with gamma2 homozygotes, who were modest drinkers, displaying 78% CHD risk reduction compared to gamma1 homozygotes (HR=0.22, 95% CI 0.05-0.94). There was, however, no association between genotype and apoAI, HDL or fibrinogen and this was not altered when alcohol intake was considered. These findings confirm that the cardiovascular benefit of modest alcohol consumption. ADH1C genotype modifies the relationship between alcohol consumption and CHD risk but at lower levels than previously reported.
authors.affiliation: Division of Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, 5 University Street, London WC1E 6JF, UK.
authors.forename: Jenan
authors.initials: J
authors.lastname: Younis
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Cooper
authors.forename: George J
authors.initials: GJ
authors.lastname: Miller
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000502:physiology*; D000428:Alcohol Drinking; D008076:Cholesterol, HDL; D003324:Coronary Artery Disease / Q000209:etiology* / Q000517:prevention & control*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D008076:Cholesterol, HDL; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase