title: Associations of estrogen receptor alpha and beta gene polymorphisms with sex steroid levels and body fat content in men.
abstract: OBJECTIVE
  Estrogens play an important role in male physiology. We investigated the possible association of four single nucleotide polymorphisms in Estrogen Receptor α ( ESR1) and Estrogen Receptor β ( ESR2) genes with circulating levels of sex steroids and Sex Hormone Binding Globulin (SHBG) in men.
  
  
  METHODS
  SHBG, total and calculated free testosterone (TT and cal FT), estradiol (E2) and free Estradiol (FE2) were determined in a population-based cohort of 170 apparently healthy Greek men. Body mass index (BMI), waist circumference (WC) and percentage of body fat (%fat) content were measured in all participants. Genotyping for the  PVU II and  XBA I polymorphisms of the  ESR1 gene and for the  RSA I and  ALU I polymorphisms of the  ESR2 gene was performed.
  
  
  RESULTS
  PVU II showed an association with E2 levels [median (IQR) pp 58.5 (42.1-73.4) pg/ml vs. Pp 48.8 (42.9-60.1) and PP 57.7 (44-70.5), p=0.032], and with %fat [mean±SD pp 24.6±5.3 vs. Pp 22.4±5.2 and PP 21.2±6.7, p=0.044], after adjustment for age and WC. Furthermore, the effect of  PVU II on E2 was independent of %fat (p=0.038). A synergistic effect of the two  ESR1 polymorphisms on E2 (p=0.023), FE2 (p=0.03) and %fat (p=0.004) was present. Finally, a synergistic effect of the  ESR1 and  ESR2 genes on TT (p=0.009), independent of age, WC and %fat also emerged.
  
  
  CONCLUSIONS
  Genetic variation in  ESR1 is associated with serum estradiol levels and body fat content regulation in men. Furthermore, a synergistic effect of  ESR1 and  ESR2 genes is exerted on serum testosterone levels.
authors.affiliation: Department of Endocrinology, University Hospital, School of Medicine, University of Thessaly, Larissa, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Sakka
authors.forename: Z A
authors.initials: ZA
authors.lastname: Efstathiadou
authors.forename: S A
authors.initials: SA
authors.lastname: Polyzos
authors.forename: M
authors.initials: M
authors.lastname: Goutou
authors.forename: N
authors.initials: N
authors.lastname: Stakias
authors.forename: G N
authors.initials: GN
authors.lastname: Koukoulis
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics*; D000328:Adult; D001823:Body Composition / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D056726:Genetic Association Studies; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006115:Greece; D006801:Humans; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011110:Polymorphism, Genetic / Q000502:physiology; D012737:Sex Factors; D055815:Young Adult
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012739:Gonadal Steroid Hormones