Do the ethanol metabolizing enzymes modify the relationship between alcohol consumption and blood pressure?

BACKGROUNDSeveral cross-sectional studies have examined whether the relationship between alcohol consumption and blood pressure (alcohol–BP relationship) differs among individuals with different aldehyde dehydrogenase-2 (ALDH2) genotypes, but few studies have examined the association with alcohol dehydrogenase-2 (ADH2), and those have yielded inconsistent results. We examined the potential modulatory effects of ADH2 and ALDH2 genotypes on the alcohol-BP relationship in a cross-sectional sample of a Japanese rural community. METHODS AND RESULTSThe study subjects were 335 randomly selected men aged 40–69 years, who lived in Shiso, a Japanese rural county, in 1999 or 2000. The genetic polymorphisms of ADH2 and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The frequencies of ADH2/2 (wild-type), 2/2 (superactive heterozygotes), and 2/2 (superactive homozygotes) were 8.4, 34.9 and 56.7%, respectively; and those of ALDH2/2 (wild-type), 2/2 (inactive heterozygotes), and 2/2 (inactive homozygotes) were 52.8, 40.9, and 6.3%, respectively. A multiple linear regression analysis showed that the relationship between alcohol consumption and diastolic blood pressure was significantly stronger in men with ADH2/2 than those with ADH2/2 or 2/2 (adjusted regression coefficient = 0.0392 versus 0.0113 mmHg for + 1 g ethanol/week, P for difference in slope = 0.018). The strength of the alcohol–BP relationship was similar in all of the ALDH2 genotype groups. CONCLUSION The alcohol–BP relationship was significantly stronger in men with ADH2/2 than in men with ADH2/2 or 2/2 in this Japanese rural population. This finding was exactly the opposite of what one previous study suggested.