Background and Purpose--Genetic polymorphism of the alcohol dehydrogenase type 3 gene (ADH1C) has recently been associated with reduced risk of myocardial infarction. However, data on risk of stroke are not available.

Methods--We examined the possible association between the ADH1C 1/2 polymorphism and risk of stroke in a prospective, nested case-control sample from the Physicians’ Health Study of 14 916 apparently healthy men who were followed over a 12-year period. A total of 320 incident stroke cases and 550 age- and smoking-matched controls were genotyped.

Results--All observed genotype frequencies were in Hardy-Weinberg equilibrium. The allele and genotype distributions of the polymorphism tested were similar between cases and controls, such that the relative risk of stroke was 1.04 for ADH1C 1/2 (95% CI=0.85 to 1.28; P=0.65) assuming an additive mode of inheritance. Contrary to prior findings for myocardial infarction, no evidence of association was observed to suggest an effect modification of ADH1C genotypes with the level of alcohol consumption on the risk of stroke. Similar findings were observed in subgroup analysis restricted to ischemic events.

Conclusions--In this large, prospective study, we found little evidence that the ADH1C 1/2 polymorphism is associated with risk of future stroke. These data raise the possibility of important pathologic differences in ischemia between the coronary and cerebral circulations.