The aldehyde dehydrogenase 2 gene is a risk factor for hypertension in Japanese but does not alter the sensitivity to pressor effects of alcohol: TheSuita Study

Excessive alcohol consumption is a potent risk factor for high blood pressu re. About half of Japanese show an extremely high sensitivity to alcohol, w hich is due to a genetic deficiency in an isoenzyme of aldehyde-dehydrogena se with a low K-m (ALDH2). It is possible that the effects of alcohol consu mption on blood pressure differ according to the ALDH2 genotype. The purpos e of the present study was to assess the influence of the ALDH2 genotype on the pressor effects of alcohol. The influence of the ALDH2 genotype on blo od pressure was investigated in a large cohort (4,000 subjects) representin g the general population in Japan. The genotype was determined by the TaqMa n method. The genotype was significantly associated with alcohol consumptio n, gamma-GTP level, and HDL cholesterol level in both males and females. Th e odds ratio for the presence of hypertension for the Glu/Glu genotype in c omparison to other genotypes was 1.67 (p< 0.0001, odds ratio=1.37-2.08, 95% confidence interval) among males. In contrast, the ALDH2 genotype had no s ignificant effects on blood pressure among females. To investigate whether the ALDH2 genotype affected the sensitivity to the pressor effects of alcoh ol, we analyzed the effects of the ALDH2 genotype (Lys/Lys + Lys/Glu=0, Glu /Glu=1) and the level of alcohol consumption on blood pressure values after adjusting for age and BMI (residuals after adjusting for age and BMI). Amo ng males, while the level of alcohol consumption significantly affected sys tolic, diastolic and pulse pressure, no significant interaction was observe d between the ALDH2 genotype and the level of alcohol consumption in determ ining blood pressure levels. These results suggest that the Glu/Glu genotyp e is a potent risk factor for hypertension among males mainly through its a ssociation with the level of alcohol consumption, and that the ALDH2 genoty pe does not affect the sensitivity to the pressor effects of alcohol.