This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gorai, I. Articles by Hirahara, F. Search for Related Content PubMed PubMed Citation Articles by Gorai, I. Articles by Hirahara, F. Pubmed/NCBI databases Gene GEO Profiles HomoloGene OMIM UniGene Substance via MeSH

Estrogen-Metabolizing Gene Polymorphisms, But Not Estrogen Receptor- Gene Polymorphisms, Are Associated with the Onset of Menarche in Healthy Postmenopausal Japanese Women

Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan

Address all correspondence and requests for reprints to: Dr. Itsuo Gorai, Department of Obstetrics and Gynecology, International University of Health and Welfare, Atami Hospital, 13-1 Higashi-Kaigancho, Atami 413-0012, Japan. E-mail: I.gorai{at}iuhw.ac.jp.

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- 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-: 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.

Abbreviations: E2, Estradiol; ER, estrogen receptor-; RFLP, restriction fragment length polymorphism.

This article has been cited by other articles:

				N. Mendoza, F. J. Moron, F. Quereda, F. Vazquez, M. C. Rivero, T. Martinez-Astorquiza, L. M. Real, R. Sanchez-Borrego, A. Gonzalez-Perez, and A. Ruiz A Digenic Combination of Polymorphisms Within ESR1 and ESR2 Genes Are Associated With Age at Menarche in the Spanish Population Reproductive Sciences, March 1, 2008; 15(3): 305 - 311. [Abstract] [PDF]

				M. E. Kevenaar, A. P.N. Themmen, F. Rivadeneira, A. G. Uitterlinden, J. S.E. Laven, N. M. van Schoor, P. Lips, H. A.P. Pols, and J. A. Visser A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity Hum. Reprod., September 1, 2007; 22(9): 2382 - 2388. [Abstract] [Full Text] [PDF]

				J. Zhao, D.-H. Xiong, Y. Guo, T.-L. Yang, R. R. Recker, and H.-W. Deng Polymorphism in the insulin-like growth factor 1 gene is associated with age at menarche in caucasian females Hum. Reprod., June 1, 2007; 22(6): 1789 - 1794. [Abstract] [Full Text] [PDF]

				B. M. Nathan, C. A. Hodges, P. J. Supelak, L. C. Burrage, J. H. Nadeau, and M. R. Palmert A Quantitative Trait Locus on Chromosome 6 Regulates the Onset of Puberty in Mice Endocrinology, November 1, 2006; 147(11): 5132 - 5138. [Abstract] [Full Text] [PDF]

				Y. Guo, D.-H. Xiong, T.-L. Yang, Y.-F. Guo, R. R. Recker, and H.-W. Deng Polymorphisms of estrogen-biosynthesis genes CYP17 and CYP19 may influence age at menarche: a genetic association study in Caucasian females Hum. Mol. Genet., August 15, 2006; 15(16): 2401 - 2408. [Abstract] [Full Text] [PDF]

				Y. Guo, H. Shen, P. Xiao, D.-H. Xiong, T.-L. Yang, Y.-F. Guo, J.-R. Long, R. R. Recker, and H.-W. Deng Genomewide Linkage Scan for Quantitative Trait Loci Underlying Variation in Age at Menarche J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1009 - 1014. [Abstract] [Full Text] [PDF]

				J-R Long, H Xu, L-J Zhao, P-Y Liu, H Shen, Y-J Liu, D-H Xiong, P Xiao, Y-Z Liu, V Dvornyk, et al. The oestrogen receptor {alpha} gene is linked and/or associated with age of menarche in different ethnic groups J. Med. Genet., October 1, 2005; 42(10): 796 - 800. [Full Text] [PDF]

				H. S. Kok, K. M. van Asselt, Y. T. van der Schouw, P. H.M. Peeters, and C. Wijmenga Genetic studies to identify genes underlying menopausal age Hum. Reprod. Update, September 1, 2005; 11(5): 483 - 493. [Abstract] [Full Text] [PDF]

				N. Xita, A. Tsatsoulis, I. Stavrou, and I. Georgiou Association of SHBG gene polymorphism with menarche Mol. Hum. Reprod., June 1, 2005; 11(6): 459 - 462. [Abstract] [Full Text] [PDF]

				L. F. Masson, L. Sharp, S. C. Cotton, and J. Little Cytochrome P-450 1A1 Gene Polymorphisms and Risk of Breast Cancer: A HuGE Review Am. J. Epidemiol., May 15, 2005; 161(10): 901 - 915. [Abstract] [Full Text] [PDF]

				L.A. Hefler, C. Grimm, G. Heinze, C. Schneeberger, M.W. Mueller, A. Muendlein, J.C. Huber, S. Leodolter, and C.B. Tempfer Estrogen-metabolizing gene polymorphisms and age at natural menopause in Caucasian women Hum. Reprod., May 1, 2005; 20(5): 1422 - 1427. [Abstract] [Full Text] [PDF]

				H. S. Kok, N. C. Onland-Moret, K. M. van Asselt, C. H. van Gils, Y. T. van der Schouw, D. E. Grobbee, and P. H.M. Peeters No association of estrogen receptor {alpha} and cytochrome P450c17{alpha} polymorphisms with age at menopause in a Dutch cohort Hum. Reprod., February 1, 2005; 20(2): 536 - 542. [Abstract] [Full Text] [PDF]

				L. Sharp, A. H. Cardy, S. C. Cotton, and J. Little CYP17 Gene Polymorphisms: Prevalence and Associations with Hormone Levels and Related Factors. A HuGE Review Am. J. Epidemiol., October 15, 2004; 160(8): 729 - 740. [Abstract] [Full Text] [PDF]

				H. Yamada, F. Sata, E. H. Kato, Y. Saijo, S. Kataoka, M. Morikawa, S. Shimada, T. Yamada, R. Kishi, and H. Minakami A polymorphism in the CYP17 gene and intrauterine fetal growth restriction Mol. Hum. Reprod., January 1, 2004; 10(1): 49 - 53. [Abstract] [Full Text] [PDF]

				A.-S. Parent, G. Teilmann, A. Juul, N. E. Skakkebaek, J. Toppari, and J.-P. Bourguignon The Timing of Normal Puberty and the Age Limits of Sexual Precocity: Variations around the World, Secular Trends, and Changes after Migration Endocr. Rev., October 1, 2003; 24(5): 668 - 693. [Abstract] [Full Text] [PDF]