title: Estrogen receptor-1 genetic polymorphisms for the risk of premature ovarian failure and early menopause.
abstract: BACKGROUND
  The aim of this study was to investigate the role of the estrogen receptor 1 (ESR1) genetic polymorphisms for early menopause that was classified as premature ovarian failure (POF) and early menopause (EM) and to examine whether the associations of ESR1 genetic variants are different for POF and EM.
  
  
  METHODS
  We selected 100 POF cases and matched 100 EM cases and 200 normal menopause (NM) controls from the Korean Multi-Center Cohort. Among them, we restricted idiopathic POF and EM cases vs NM controls by excluding POF/EM cases with medical/surgical causes. The XbaI (rs9340799) and PvuII (rs2234693) in the ESR1 gene were genotyped. The single-nucleotide polymorphism (SNP) and haplotype effects were analyzed by multivariate logistic regression and haplotype analysis. Also nominal polytomous logistic regression was used to find whether ESR1 genetic variants are differently associated with POF and EM.
  
  
  RESULTS
  The global p values for idiopathic POF and EM were 0.08 and 0.39 (SNP-based), and <0.001 and 0.12 (haplotype-based), respectively. The XbaI genetic variant containing the X allele was marginally significantly associated with a reduced risk of idiopathic POF (OR = 0.6, 95% CI 0.3-1.0). The P-x haplotype and diplotypes significantly decreased the risk of idiopathic POF (OR = 0.5, 95% CI 0.2-0.9; OR = 0.4, 95% CI 0.2-0.9, respectively). In contrast from POF, the P-x haplotypes and diplotypes insignificantly increased the risk for both idiopathic EM (p(polytomous) = 0.009 for P-x haplotype; p(polytomous) = 0.02 for P-x diplotypes).
  
  
  CONCLUSIONS
  Our results suggest that the ESR1 gene including PvuII and XbaI polymorphisms may modify the risk of idiopathic premature ovarian failure (POF) but not idiopathic early menopause (EM) risk.
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Yang
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Cho
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Lim
authors.forename: Kwang-Pil
authors.initials: KP
authors.lastname: Ko
authors.forename: Kun-Sei
authors.initials: KS
authors.lastname: Lee
authors.forename: Hyeongsu
authors.initials: H
authors.lastname: Kim
authors.forename: Sung Vin
authors.initials: SV
authors.lastname: Yim
authors.forename: Soung Hoon
authors.initials: SH
authors.lastname: Chang
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
mesh_terms: D000328:Adult; D015331:Cohort Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D008594:Menopause, Premature / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D011446:Prospective Studies; D056910:Republic of Korea; D012306:Risk
chemical_list: D047628:Estrogen Receptor alpha