We analyzed the association of 2 biallelic polymorphisms of CYP11B2 (P450c1
1AS) 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 nor
motensive subjects. The association between low-renin hypertension and angi
otensin I-converting enzyme (ACE) gene was also analyzed. An elevated ratio
of plasma aldosterone concentration to plasma renin activity was used to i
dentify low-renin hypertension. Genotypes for CYP11B2 and ACE were determin
ed through polymerase chain reactions. The Arg(173) allele frequency did no
t differ between hypertensive patients considered as 1 group (34%) and norm
otensive control subjects (37%). However, only 22% of 58 CYP11B2 alleles st
udied in 29 patients with low-renin hypertension were Arg(173) alleles, whe
reas 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 linkag
e 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 compar
ed with those with normal- or high-renin hypertension. Deletion (D) allele
frequencies of the ACE gene were 31% in the patients with low-renin hyperte
nsion, 39% in the patients with normal- or high-renin hypertension, and 29%
in normotensive control subjects. We detected an association between the C
YP11B2 gene polymorphisms and low-renin hypertension with inappropriate ele
vation of aldosterone. The decreased frequencies of the Arg(173) and -344C
variants in the CYP11B2 appear to be genetically linked to low-renin hypert
ension in the Japanese population studied.