Alpha-adducin Gly460Trp polymorphism is associated with low renin hypertension in younger subjects in the Ohasama study

Background The Gly460Trp polymorphism of the alpha-adducin gene (ADD-1) has been examined as a candidate gene for essential hypertension with salt sensitivity in the Caucasian population. However, we failed to detect a positive association between the Gly460Trp polymorphism of ADD-1 and hypertension in a small series of Japanese subjects. Objective To examine the precise association between the Gly460Trp polymorphism of ADD-1 and blood pressure (BP), we carried out an association study using a Japanese population: the Ohasama Study. Design Subjects (n = 1490) were recruited from participants in the Ohasama Study, which is a cohort in a rural community of northern Japan. Methods DNA was extracted from the buffy coat of the participants who gave informed consent for genetic analysis, and the Gly460Trp polymorphism of ADD-1 was determined by the TaqMan polymerase chain reaction method. Various BID values (casual BP, ambulatory BID and home BP) were measured in the Ohasama study. We used the mean values of these BID measurements for analysis. Results The frequencies of genotypes in the Ohasama population were 23% Gly/Gly, 49% Gly/Trp, and 28% Trp/Trp. In the baseline characteristics, age, sex, body mass index, frequency of diabetes and hyperlipidemia were significantly different between hypertensive or normotensive subjects. In total subjects, all BID values were not different among ADD-1 genotypes. In the younger subjects (< 60 years old) with low plasma renin activity (< 1.0 ng/ml per h), however, ambulatory BP and home BP were significantly higher in the subjects with the Gly/Trp or Trp/Trp genotypes of ADD-1 polymorphism than in those with the Gly/Gly genotype. In the same population, the frequency of the Gly/Trp or Trp/Trp genotypes of ADD-1 was significantly higher in hypertensives than in normotensives (83 versus 72%, chi(1)(2) = 4.04, P < 0.05; odds ratio, 2.12; 95% confidence interval, 1.02-4.68). Conclusions These findings suggest the possibility that the Gly460Trp polymorphism of ADD-1 is associated with low renin hypertension. (C) 2002 Lippincott Williams Wilkins.