title: Risk of premature ovarian failure is associated to the PvuII polymorphism at estrogen receptor gene ESR1.
abstract: OBJECTIVE
  Estrogen plays an important role in the human reproductive system and it action is mediated mainly by two specific receptors: α (ERα) and β (ERβ). There were described polymorphic variants in ESR1 and ESR2 genes and studies showed controversial results regarding their association with premature ovarian failure. We aimed to determine the prevalence of ESR1 and ESR2 polymorphisms in Brazilian patients and controls. After associate the polymorphisms with premature ovarian failure (POF).
  
  
  METHODS
  Genetic association study was performed with 70 women with POF and 73 normally menopaused controls. Detection of ESR1 (PvuII/and XbaI) and ESR2 (AluI and RsaI) gene polymorphisms were performed using TaqMan PCR. The single-nucleotide polymorphism (SNPs) and haplotype effects were analyzed by multivariate logistic regression and haplotype analysis and a p-value < 0.05 was considered significant.
  
  
  RESULTS
  Individual SNP analysis revealed that PvuII polymorphism was statistically associated with POF (p = 0.034) under a recessive model. Regarding XbaI, AluI and RsaI SNPs, no statistical difference was observed between POF group and controls (p = 0.575, p = 0.258 and p = 0.483, respectively). Combined genotypes of ESR1 and ESR2 polymorphisms did not identify a risk haplotype associated with POF.
  
  
  CONCLUSIONS
  In Brazilian population evaluated results have demonstrated that the genetic variation in ESR1 gene (PvuII polymorphism) is associated to POF risk.
authors.affiliation: Department of Gynecology and Obstetrics, Faculdade de Medicina do ABC, Division of Human Reproduction and Genetics, Avenida Príncipe de Gales, 821, Santo André, SP, Brazil 09060-650.
authors.forename: Emerson Barchi
authors.initials: EB
authors.lastname: Cordts
authors.forename: Aline Amaro
authors.initials: AA
authors.lastname: Santos
authors.forename: Carla
authors.initials: C
authors.lastname: Peluso
authors.forename: Bianca
authors.initials: B
authors.lastname: Bianco
authors.forename: Caio Parente
authors.initials: CP
authors.lastname: Barbosa
authors.forename: Denise Maria
authors.initials: DM
authors.lastname: Christofolini
mesh_terms: D000328:Adult; D001938:Brazil; D015257:DNA-Cytosine Methylases / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D004967:Estrogens / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D012307:Risk Factors
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; C047084:DNA modification methylase PvuII; D015257:DNA-Cytosine Methylases