title: CYP11B2 polymorphisms and home blood pressure in a population-based cohort in Japanese: the Ohasama study.
abstract: Genetic polymorphisms of the aldosterone synthase gene (CYP11B2) have been major targets of studies into the genetic factors involved in hypertension. We have identified three genetic variants of CYP11B2, -344C/T at the promoter region, a conversion in intron 2 from the CYP11B2 sequence to the CYP11B1 sequence, and R173K in exon 3, in the Japanese population. -344C/T and R173K were in complete linkage disequilibrium in CYP11B2, and -344C/T was in strong, but not complete, linkage disequilibrium with the polymorphism in intron 2. Thus, two genetic polymorphisms, -344C/T and the gene conversion in intron 2, were investigated in association with home blood pressure (BP) values and clinical parameters in 1,242 subjects aged 40 and over in Ohasama, a rural Japanese community. Hypertension was defined as being treated with antihypertensive medication and/or having home BP values of more than 135 mmHg in systole and/or 85 mmHg in diastole. The results demonstrated that the -344T allele was significantly associated with increased prevalence of hypertension (p=0.015 in multiple logistic regression analysis, adjusted by age, gender, BMI, and smoking status), though BP level was unaltered. This allele was also significantly related to the prevalence of cardiovascular diseases in the older population (60 < or = age, p=0.014). The resting polymorphism, a gene conversion in CYP11B2 intron 2, was not associated with any clinical parameters. Therefore, -344C/T polymorphism in CYP11B2 was considered an independent genetic factor possibly associated with hypertension or atherosclerotic diseases in the Japanese population.
authors.affiliation: Division of Molecular Medicine and Gene Transfer Research, Center for Translational and Advanced Animal Research on Human Diseases, Tohoku University School of Medicine, Sendai, Japan. mmitsu2i@mail.cc.tohoku.ac.jp
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Matsubara
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sato
authors.forename: Takuya
authors.initials: T
authors.lastname: Nishimura
authors.forename: Michiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kikuya
authors.forename: Hirohito
authors.initials: H
authors.lastname: Metoki
authors.forename: Mari
authors.initials: M
authors.lastname: Michimata
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tsuji
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imai
mesh_terms: D000368:Aged; D001161:Arteriosclerosis / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D001795:Blood Pressure Determination; D015331:Cohort Studies; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000235:genetics*; D007438:Introns; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D019405:Cytochrome P-450 CYP11B2