CYP11B2 gene haplotypes independently and in concurrence with aldosterone and aldosterone to renin ratio increase the risk of hypertension.

OBJECTIVES Aldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure. Polymorphisms in aldosterone-synthase gene (CYP11B2) may associate with heterogeneous aldosterone production and hypertension. Hence, we investigated -344T/C, Iw/Ic polymorphisms of CYP11B2, plasma renin activity (PRA) and aldosterone concentration (PAC). DESIGN AND METHODS Consecutive ethnically-matched 450 hypertensive patients and 360 controls were screened by PCR-RFLP for genotypes and haplotypes; PRA and PAC were measured. RESULTS The Iw/Ic polymorphism distribution differed significantly between the two groups (LRT chi(2)=15.8, df=2, P=0.000). The mutant allele-Ic and genotype-Ic/Ic were overrepresented in patients (35% versus 27% and 13% versus 7%). Overrepresentation of T-Ic haplotype in patients was identified as risk haplotype (P=0.000). Patients had significantly higher PAC and aldosterone-to-renin ratio (ARR; P=0.000), which was Ic-allele dependent. CONCLUSIONS The haplotype T-Ic associated with hypertension susceptibility. Correlation between Ic-allele and raised ARR likely serve in hypertension management.