Lys(173)Arg and -344T/C variants of CYP11B2 in Japanese patients with low-renin hypertension.

We analyzed the association of 2 biallelic polymorphisms of CYP11B2 (P450c11AS) gene (1 in the Lys(173)Arg of exon 3 and the other in the promoter at position -344T/C) with hypertension in 73 hypertensive patients and 134 normotensive subjects. The association between low-renin hypertension and angiotensin I-converting enzyme (ACE) gene was also analyzed. An elevated ratio of plasma aldosterone concentration to plasma renin activity was used to identify low-renin hypertension. Genotypes for CYP11B2 and ACE were determined through polymerase chain reactions. The Arg(173) allele frequency did not differ between hypertensive patients considered as 1 group (34%) and normotensive control subjects (37%). However, only 22% of 58 CYP11B2 alleles studied in 29 patients with low-renin hypertension were Arg(173) alleles, whereas the frequency of this allele was 41% in patients with normal- or high-renin hypertension (P=0.033). An analysis of the distribution of -344C and Arg(173) genotypes indicated that these 2 variants were in complete linkage disequilibrium: -344C was present in a subset of chromosomes carrying the Arg(173) (P<0.001 in low-renin hypertension). Therefore, the frequency of the -344C allele was low in the patients with low-renin hypertension compared with those with normal- or high-renin hypertension. Deletion (D) allele frequencies of the ACE gene were 31% in the patients with low-renin hypertension, 39% in the patients with normal- or high-renin hypertension, and 29% in normotensive control subjects. We detected an association between the CYP11B2 gene polymorphisms and low-renin hypertension with inappropriate elevation of aldosterone. The decreased frequencies of the Arg(173) and -344C variants in the CYP11B2 appear to be genetically linked to low-renin hypertension in the Japanese population studied.