Genetic polymorphisms in alcohol metabolizing enzyme and alcohol-induced health effects.

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Three-hundred-and-sixty-seven unrelated Japanese male workers aged between 36 and 61 years were analyzed for the genotypes of cytochrome P450 2E1 (CYP2E1), and the association with alcohol-related health effects including blood pressure (BP) elevation. Homozygous for the cl (wild) gene was found in 204 men (55%), homozygous for the c2 (variant) gene in 17 (5%), and heterozygous in 146 (40%). Arithmetic means of alcohol consumed per week in the genotypes of cl/cl, cl/c2 and c2/c2 were 218,257 and 211g, respectively, and were not statistically different. BP was elevated with the increase in alcohol consumption, and was significantly higher in the c2/c2 genotype than in the other genotypes among the subjects consuming 200g or more of alcohol per week. Serum uric acid did not correlate with alcohol consumption in the whole subjects, but it was also higher in drinkers having the c2/c2 genotype. Although the number of subjects was too small for a definite conclusion to be drawn, these results suggest to some extent that Japanese men having the c2/c2 genotype of CYP2E1 are more sensitive to the pressor effect of alcohol. Further studies are required to confirm this. Key words : alcohol, blood pressure, cytochrome P450 2E1, genotype, Japanese.