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.
Keywords
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Article Info
Publication History
Accepted:
December 10,
2004
Received in revised form:
December 9,
2004
Received:
August 18,
2004
Identification
Copyright
© 2004 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
