title: Association of polymorphisms in estrogen receptors (ESR1 and ESR2) with male infertility: a meta-analysis and systematic review.
abstract: OBJECTIVE
  Estrogens play an important role in male reproduction via interacting with estrogen receptors (ERs), whose expression can be regulated by the polymorphisms in different regions of ESR1 and ESR2 genes. However, results from published studies on the association between four well-characterized polymorphisms (PvuII, XbaI, RsaI, and AluI) in the gene of ERs (ESR1 and ESR2) and male infertility risk are inconclusive.
  
  
  METHODS
  To investigate the strength of relationship of PvuII and XbaI in ESR1 and RsaI and AluI in ESR2 with male infertility, we conducted a meta-analysis of 12 eligible studies with odds ratio (OR) and its corresponding 95 % confidence intervals (95 % CI).
  
  
  RESULTS
  Overall, ESR1 PvuII and ESR2 RsaI polymorphisms were significantly associated with male infertility risk. The subgroup analyses by ethnicities demonstrated that in Asians, ESR1 PvuII, XbaI and ESR2 RsaI polymorphisms were significantly associated with a decreased infertility risk, while in Caucasians both ESR1 PvuII and ESR2 RsaI polymorphisms increased the susceptibility to male infertility. As for ESR2 AluI polymorphism, no significant association was detected in either overall analysis or subgroup analyses by ethnicities/genotyping methods.
  
  
  CONCLUSIONS
  This meta-analysis suggested that polymorphisms in the genes of ERs (ESR1 and ESR2) may have differential roles in the predisposition to male infertility according to the different ethnic backgrounds. Further well-designed and unbiased studies with larger sample size and diverse ethnic backgrounds should be conducted to verify our findings.
authors.affiliation: Department of Urology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China.
authors.forename: Yu-Zheng
authors.initials: YZ
authors.lastname: Ge
authors.forename: Lu-Wei
authors.initials: LW
authors.lastname: Xu
authors.forename: Rui-Peng
authors.initials: RP
authors.lastname: Jia
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Li
authors.forename: Ran
authors.initials: R
authors.lastname: Wu
authors.forename: Sheng
authors.initials: S
authors.lastname: Liao
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.forename: Si-Jia
authors.initials: SJ
authors.lastname: Tan
authors.forename: Qun
authors.initials: Q
authors.lastname: Song
authors.forename: Hui
authors.initials: H
authors.lastname: Xin
mesh_terms: D044466:Asian People / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C024669:endodeoxyribonuclease AluI; C061224:endodeoxyribonuclease PvuI; C025580:endodeoxyribonuclease XBAI; D015252:Deoxyribonucleases, Type II Site-Specific; C040158:GTAC-specific type II deoxyribonucleases