Genetic Polymorphism of CYP11B2 Gene and Hypertension in Japanese

Low-renin hypertension is characterized by a high ratio of aldosterone to plasma renin activity (ALD/PRA), which may suggest inappropriately increased aldosterone biosynthesis. The genes for the enzymes involved in aldosterone synthesis may contribute to low-renin hypertension. We investigated the associations between genetic variations of CYP11B2 (aldosterone synthase) T(-344)C and hypertension in 482 Japanese subjects. Subjects older than 50 years with a blood pressure 160/95 mm Hg were considered hypertensive (n=255 subjects). The frequency of the TC+CC genotypes in the normotensive group was significantly lower than in the hypertensive group. Logistic analysis on 482 subjects revealed that body mass index, gender, and the genotype of CYP11B2 T(-344)C were significantly associated with hypertension. ALD and PRA were assessed in 97 subjects with hypertension, and the TC+CC genotypes were significantly associated with higher ALD/PRA. Sixty-five subjects with hypertension were assessed by 24-hour ambulatory blood pressure monitoring, and the frequency of nondippers (a difference in mean blood pressure of <10% between the daytime 6 AM to 9 PM and nighttime 9 PM to 6 AM hours) was significantly higher in subjects with the TC+CC (hetero+homo mutation) genotype than in subjects with the TT (wild-type) genotype. Echocardiographic assessment (n=136) revealed that the ratio of left ventricular end-diastolic dimension to height tended to be higher in subjects with the TC+CC genotype than in subjects with the TT genotype. The present study suggests that the (-344)C allele of the CYP11B2 gene may be a genetic marker for low-renin hypertension in Japanese.