Blood pressure in relation to three candidate genes in a Chinese population

Objective: In a prospective analysis of a Caucasian population, we recently found that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), α-adducin (Gly460Trp) and aldosterone synthase (-344C/ T) jointly influence the incidence of hypertension. We therefore investigated the association between blood pressure and these three genes in a Chinese population. Methods: We genotyped 479 Han Chinese from 125 nuclear families recruited in northern China via random sampling (∼75%) and at specialized hypertension clinics (∼25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and the quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables. Results: The participants included 239 (49.9%) women and 132 (27.6%) hypertensive patients, of whom 77 took antihypertensive drugs. The blood pressure, measured at the subjects' homes, averaged 126/80 mmHg. Mean values of urinary sodium, potassium and Na⁺/K⁺ ratio were 226 mmol/day, 37 mmol/day and 6.31, respectively. In adjusted GEE analyses, systolic blood pressure was 9.3 mmHg (95% confidence interval 3.6-15.0 mmHg; P = 0.001) and 14.6 mmHg (95% confidence interval 3.4-25.8 mmHg; P = 0.01) higher in the ACE DD than II subjects among the α-adducin TrpTrp (n = 141) and aldosterone synthase CC (n = 33) homozygotes, respectively (P ≤ 0.05 for interactions of the ACE genotype with the α-adducin and aldosterone synthase polymorphisms). Among 40 informative offspring homozygous for the α-adducin Trp allele, systolic blood pressure was significantly associated with transmission of the ACE D allele (β = 5.5 mmHg; P = 0.046). Conclusions: The ACE I/D, α-adducin Gly460Trp and aldosterone synthase -344C/T polymorphisms interact to influence systolic blood pressure in Chinese, suggesting that these genes might indeed predispose to hypertension, especially in an ecogenetic context characterized by a high salt intake.