title: ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure.
abstract: BACKGROUND
  Premature ovarian failure (POF) is a complex and heterogeneous disorder that is influenced by multiple genetic components. Numerous candidate gene studies designed to identify POF susceptibility loci have been published, but most positive findings have not been confirmed in follow up studies. We sought to determine if sequence variants previously associated with age at natural menopause (AANM) or early menopause (EM) contribute as well to genetic susceptibility to POF.
  
  
  METHODS
  Our study was performed on 371 unrelated idiopathic women with POF and 800 women controls, all Chinese Han. Thirty six SNPs from previous genome-wide association studies (GWAS) responsible for AANM or EM and 3 additional SNPs in ESR1, and 2 additional SNPs in PTHB1 were tested using the Sequenom MassARRAY iPLEX platform for genotyping.
  
  
  RESULTS
  Three SNPs - rs2278493 in HK3, rs2234693 in ESR1 and rs12611091 in BRSK1 - showed nominally significant association with POF. Thus, a plausible relationship could exist between ESR1, BRSK1, HK3 and POF.
  
  
  CONCLUSIONS
  This largest association study undertaken to determine correlation between POF and AANM/EM revealed three significant SNPs (rs2278493, rs2234693, and rs12611091). All are associated with not only AAWM and EM but also POF. Insights into shared genetic susceptibility between POF and AANM/EM will provide novel entry points for unraveling genetic mechanism involved in ovarian reserve and oocyte aging processes.
authors.affiliation: Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Qin
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: You
authors.forename: Deying
authors.initials: D
authors.lastname: Wei
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D001630:Bezoars / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D017219:Gastric Outlet Obstruction / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007223:Infant; D008892:Milk / Q000737:chemistry*