title: Mutation of the follicle-stimulating hormone receptor gene 5'-untranslated region associated with female hypertension.
abstract: Inactivating mutations in the follicle-stimulating hormone receptor (FSHR) gene have been reported to cause hereditary hypergonadotropic ovarian failure. It has been found recently that the FSHR knockout mouse exhibits hypertension. The aim of the present study was to investigate the association between polymorphisms in the human FSHR gene and essential hypertension (EH) by using single nucleotide polymorphisms (SNPs). We selected 5 SNPs in the gene (rs1394205, rs2055571, rs11692782, rs1007541, and rs2268361) and performed 2 genetic case-control studies in different populations. A confirmative case-control study was performed using 1035 EH patients and 1058 age-matched controls. Transcriptional activities were measured with a luciferase assay system. The first case-control study found that the A allele of rs1394205 was significantly higher in EH females (P=0.010). In addition, in the confirmative case-control study, there was a significant difference for this SNP between female normotensive subjects (44.5%) and EH patients (50.7%) (P=0.043). Multiple logistic regression analysis in female subjects also revealed a significant association of subjects with the A allele of rs1394205 with EH (P=0.033), with the odds ratio calculated as 1.68 (95% CI: 1.04 to 2.73). Transcriptional activity of the A allele was 56+/-8% (mean+/-SD) of that observed for the G-type allele (P=0.001). Serum estradiol levels were significantly lower in patients with the A/A genotype than in patients without the A/A genotype (P=0.004). The SNP in the 5'-untranslated region of the FSHR gene affects levels of transcriptional activity and is a susceptibility mutation of EH in women.
authors.affiliation: Division of Molecular Diagnostics, Advanced Medical Research Center, Nihon University School of Medicine, Ooyaguchi-kamimachi, 30-1 Itabashi-ku, Tokyo 173-8610, Japan. tnakayam@med.nihon-u.ac.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kuroi
authors.forename: Morihiko
authors.initials: M
authors.lastname: Sano
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Makita
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamada
authors.forename: Norio
authors.initials: N
authors.lastname: Takahashi
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Hirawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
mesh_terms: D020121:5' Untranslated Regions; D000368:Aged; D000818:Animals; D016466:CHO Cells; D016022:Case-Control Studies; D006224:Cricetinae; D003412:Cricetulus; D004958:Estradiol / Q000097:blood; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011962:Receptors, FSH / Q000235:genetics*; D012727:Sex Characteristics; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D011962:Receptors, FSH; D004958:Estradiol