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. Design and 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 Pvull 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 AA 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. (C) 2015 Elsevier Inc. All rights reserved.