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雌激素受体 alpha 和 Beta 基因多态性与男性血脂水平和胰岛素抵抗的关系。

Associations of estrogen receptor alpha and Beta gene polymorphisms with lipid levels and insulin resistance in men.

机构信息

Endocrine Clinic, "Hippokration" General Hospital of Thessaloniki, Thessaloniki, Greece.

Department of Endocrinology, University of Thessaly School of Medicine, Larissa, Greece.

出版信息

Metabolism. 2015 May;64(5):611-7. doi: 10.1016/j.metabol.2015.01.006. Epub 2015 Jan 22.

DOI:10.1016/j.metabol.2015.01.006
PMID:25665486
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 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.

摘要

目的

研究雌激素受体 alpha(ESR1)和 beta(ESR2)基因中的四个单核苷酸多态性与男性血脂水平和胰岛素抵抗的关系。

方法和设计

对 170 名希腊中年男性进行了一项基于人群的横断面队列研究,测定了血脂、葡萄糖、胰岛素和 HOMA-IR,同时还测定了体重指数(BMI)、腰围(WC)和体脂百分比(%fat)。对 ESR1 的 PvuII 和 XbaI 多态性和 ESR2 的 RsaI 和 AluI 多态性进行了基因分型。

结果

AluI 与 LDL-Chol(均值 ± 标准差,aa 4.3 ± 1.1 vs. Aa 3.7 ± 1.0 和 ΑΑ 4.2 ± 1.1,p = 0.023)和 RsaI 与 HOMA-IR [中位数(IQR),RR 1.55(0.88-2.49)vs. Rr/rr 1.69(0.72-2.29),p = 0.032]存在相关性。还发现 ESR2 基因的 RsaI 和 AluI 之间存在 LDL-Chol 水平、%fat 和 WC 的协同作用,以及 ESR1 和 ESR2 基因之间存在 TChol(p = 0.01)和 LDL-Chol(p = 0.027)水平的协同作用。这些发现在校正了潜在混杂因素后仍然具有统计学意义。PvuII 与 %fat (均值 ± 标准差,pp 24.6 ± 5.3 vs Pp 22.4 ± 5.2 和 PP 21.2 ± 6.7,p = 0.044),RsaI 与 %fat(RR 22.6 ± 5.5 vs. Rr/rr 25.2 ± 6.3,p = 0.015)和 WC(均值 ± 标准差,RR 97.4 ± 10.4 vs. Rr/rr 102.6 ± 12.6,p = 0.013)之间存在独立相关性。还发现 ESR1 多态性之间(p = 0.004)、ESR2 多态性之间以及所有四种 ESR 多态性之间存在协同作用。

结论

ESR2 与男性血脂水平和 HOMA-IR 独立于混杂因素有关。脂肪受到两种基因的影响。此外,还显示 ESR1 和 ESR2 对 TChol、LDL-Chol 和 %fat 有协同作用。

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