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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

  • Jenan Younis
    Affiliations
    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
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  • Jackie A. Cooper
    Affiliations
    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
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  • George J. Miller
    Affiliations
    Medical Research Council Cardiovascular Group, Department of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Charterhouse Square, London EC1M 6BQ, UK
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  • Steve E. Humphries
    Affiliations
    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
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  • Philippa J. Talmud
    Correspondence
    Corresponding author. Tel.: +44 20 7679 6968; fax: +44 20 7679 6212.
    Affiliations
    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
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      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 γ1 > γ2 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 γ2 homozygotes, who were modest drinkers, displaying 78% CHD risk reduction compared to γ1 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.

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