title: Lys(173)Arg and -344T/C variants of CYP11B2 in Japanese patients with low-renin hypertension.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, University of the Ryukyus School of Medicine, Nishihara, Okinawa, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Komiya
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Takara
authors.forename: T
authors.initials: T
authors.lastname: Asawa
authors.forename: M
authors.initials: M
authors.lastname: Shimabukuro
authors.forename: T
authors.initials: T
authors.lastname: Nishimori
authors.forename: N
authors.initials: N
authors.lastname: Takasu
mesh_terms: D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000483:Alleles; D001120:Arginine; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005819:Genetic Markers; D006801:Humans; D006977:Hypertension, Renal / Q000097:blood* / Q000235:genetics*; D007564:Japan; D008239:Lysine; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000502:physiology; D012083:Renin / Q000097:blood*; D012084:Renin-Angiotensin System / Q000235:genetics
chemical_list: D005819:Genetic Markers; D000450:Aldosterone; D001120:Arginine; D019405:Cytochrome P-450 CYP11B2; D012083:Renin; D008239:Lysine