Haplotypes of aldosterone synthase (CYP11132) gene in the general population of Japan: The Ohasama study

Since the identification of a chimeric aldosterone synthase which induces m endelian hypertension, polymorphisms in aldosterone synthase (CYP11B2) has been one of major targets for molecular analyses in association with hypert ension. To date, four polymorphic variants of CYP11B2, -344T/C at promoter region, a gene conversion in intron 2, 2713A/G (in exon 3) which converts f rom Lys to Arg at codon 173 (K173R), and 4986T/C (in exon7) which converts from Val to Ala at codon 386 (V386A), have been identified in Caucasian pop ulation. Then, linkage disequilibrium between -344T/C polymorphism and a ge ne conversion in intron 2 or K173R mutation has been described, suggesting the presence of genetic haplotypes in Caucasians. Since the presence of a g ene conversion in intron 2 or V386A mutation was still unknown in the Japan ese population, all these polymorphisms were examined together to determine the CYP11B2 haplotypes of Japanese, using DNA samples from 1290 participan ts of the Ohasama study, who represent the general population of a rural co mmunity of northern Japan. Molecular analyses demonstrated the presence of a gene conversion of intron 2, but the absence of V386A mutation in Japanes e population. The complete linkage disequilibrium between -344T/C polymorph ism and K173R mutation was noted. Although -344T allele was linked either w ith a gene conversion in intron 2 or with normal intron 2, -344C allele was completely linked with normal intron 2. These results indicate the presenc e of 3 allelic haplotypes of CYP11B2, -344C with normal intron 2 and 173R, -344T with normal intron 2 and 173K, and -344T with converted intron 2 and 173K, in the general Japanese population. The frequency (total 1.0) was 0.3 5, 0.53, and 0.12, respectively. The presence of allelic haplotypes is cons idered to be an additional genetic information to individual polymorphism o f CYP11B2 to determine the linkage between CYP11B2 polymorphisms and hypert ension.