title: Estrogen-metabolizing gene polymorphisms, but not estrogen receptor-alpha gene polymorphisms, are associated with the onset of menarche in healthy postmenopausal Japanese women.
abstract: Both onset and cessation of menstruation have strong genetic inclination. We aimed to identify genetic factors influencing the onset of menarche and natural menopause in a Japanese population by investigating the polymorphisms of estrogen receptor-alpha and estrogen-metabolizing enzyme genes. Three hundred seventeen postmenopausal Japanese women, aged 46 yr and over, were enrolled in this study under informed consent. Genomic DNA was extracted from peripheral leukocytes, and PCR-based restriction fragment length polymorphism assays were used to determine estrogen receptor-alpha: PvuII, XbaI, and estrogen-metabolizing enzymes; CYP17, estrogen biosynthesis (high activity, A2/A2, CYP1A1), hydroxylation (high inducibility, vt/vt, and COMT), inactivation (low activity, L/L) genotypes. There were no significant differences in ages at menarche and natural menopause or years of menstruation among each PvuII or XbaI genotype and seven combinations of PvuII and XbaI genotypes. We found that ages at menarche in women with A1/A2 (higher activity of CYP17; 13.6 +/- 1.2 yr) were significantly earlier than in those with A1/A1 (lower activity of CYP17; 14.1 +/- 1.3 yr). There were no significant differences in age at natural menopause and years of menstruation among each CYP17, CYP1A1, or COMT genotype. The small sample size of each combination of estrogen-metabolizing genotypes made it impractical to evaluate the effects of the interdependency of each genotype, including extreme genotype categories such as A2/A2L/Lvt/vt vs. A1/A1H/Hwt/wt genotypes, on ages at menarche and/or natural menopause. The results suggest that the estrogen-metabolizing CYP17 genotype influences age at menarche in healthy postmenopausal Japanese women.
authors.affiliation: Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan. I.gorai@iuhw.ac.jp
authors.forename: Itsuo
authors.initials: I
authors.lastname: Gorai
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Mae
authors.initials: M
authors.lastname: Inada
authors.forename: Hiroko
authors.initials: H
authors.lastname: Morinaga
authors.forename: Yukimi
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Kikuchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Chaki
authors.forename: Fumiki
authors.initials: F
authors.lastname: Hirahara
mesh_terms: D000368:Aged; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D047628:Estrogen Receptor alpha; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D008572:Menarche / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D019363:Cytochrome P-450 CYP1A1; D013254:Steroid 17-alpha-Hydroxylase; D008780:Methyltransferases; C019608:caffeate O-methyltransferase