title: Associations of estrogen receptor alpha and Beta gene polymorphisms with lipid levels and insulin resistance in men.
abstract: OBJECTIVE
  The association of four single nucleotide polymorphisms in estrogen receptor alpha (ESR1) and beta (ESR2) genes with lipid levels and insulin resistance in men.
  
  
  METHODS
  Lipids, glucose, insulin and HOMA-IR were determined, in a population-based, cross-sectional, cohort of 170 apparently healthy middle-aged Greek men, along with body mass index (BMI), waist circumference (WC) and percentage of body fat content (%fat). Genotyping of ESR1 for PvuII and XbaI and ESR2 for RsaI and AluI polymorphisms was performed.
  
  
  RESULTS
  Associations of AluI with LDL-Chol (mean ± SD, aa 4.3 ± 1.1 vs. Aa 3.7 ± 1.0 and ΑΑ 4.2 ± 1.1, p = 0.023) and RsaI with HOMA-IR [median (IQR), RR 1.55 (0.88-2.49) vs. Rr/rr 1.69 (0.72-2.29), p = 0.032] were found. Synergistic effects of RsaI and AluI of ESR2 gene on LDL-Chol levels, %fat and WC, as well as a synergistic effect of both ESR1 and ESR2 genes on levels of TChol (p = 0.01) and LDL-Chol (p = 0.027) were also shown. These findings remained significant after adjustment for potential confounders. Significant independent associations of PvuII with %fat (mean ± SD, pp 24.6 ± 5.3 vs Pp 22.4 ± 5.2 and PP 21.2 ± 6.7, p = 0.044), and RsaI with %fat (RR 22.6 ± 5.5 vs. Rr/rr 25.2 ± 6.3, p = 0.015) and WC (mean ± SD, RR 97.4 ± 10.4 vs. Rr/rr 102.6 ± 12.6, p = 0.013) were found. Synergistic effects on %fat, between the ESR1 polymorphisms (p = 0.004), between the ESR2 polymorphisms and among all four ESR polymorphisms studied were also present.
  
  
  CONCLUSIONS
  ESR2 is associated with LDL-Chol levels and HOMA-IR in men independently of confounders. Body fat is affected by both genes. Furthermore, a synergistic effect of ESR1 and ESR2 on TChol, LDL-Chol and %fat, was shown.
authors: Endocrine Clinic, "Hippokration" General Hospital of Thessaloniki, Thessaloniki, Greece. Electronic address: zefsta@endo.gr.
authors: Zoe A
authors: ZA
authors: Efstathiadou
authors: Department of Endocrinology, University of Thessaly School of Medicine, Larissa, Greece.
authors: Christina
authors: C
authors: Sakka
authors: Endocrine Clinic, "Hippokration" General Hospital of Thessaloniki, Thessaloniki, Greece.
authors: Stergios A
authors: SA
authors: Polyzos
authors: Department of Endocrinology, University of Thessaly School of Medicine, Larissa, Greece.
authors: Maria
authors: M
authors: Goutou
authors: Department of Endocrinology, University of Thessaly School of Medicine, Larissa, Greece.
authors: Nikolaos
authors: N
authors: Stakias
authors: Department of Endocrinology, University of Thessaly School of Medicine, Larissa, Greece.
authors: Alexandra
authors: A
authors: Bargiota
authors: Department of Endocrinology, University of Thessaly School of Medicine, Larissa, Greece.
authors: George N
authors: GN
authors: Koukoulis
mesh_terms: D001823:Body Composition; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005838:Genotype; D006115:Greece; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055105:Waist Circumference; D055815:Young Adult
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D002784:Cholesterol
keywords: Estrogen receptors; Genetic polymorphisms; HOMA; Insulin resistance; Serum lipids