Associations of ESR1 and ESR2 gene polymorphisms with metabolic syndrome and its components in postmenopausal women

Highlights

• Particular allels at three polymorphisms in the ESR1 gene (rs2234693, rs6902771, rs7774230) and one polymorphism in the ESR2 gene (rs3020449) may impact the development of metabolic syndrome.

• Some of the ESRs polymorphisms (rs2234693, rs6902771, rs7774230, rs3020449) may influence serum cholesterol concentrations in women after menopause.

Abstract

Objectives

Metabolic syndrome (MS) affects a quarter of Polish people and is associated with diabetes mellitus type 2 and ischemic heart disease. The prevalence of MS in postmenopausal women can be increased by the lack of protective effects of oestrogens. In the near future, because of the general increase in life expectancy, the number of postmenopausal women will rise substantially. Therefore, investigating both the environmental and the genetic factors predisposing to MS may have a great impact on women’s health. The aim of this study was to determine whether particular oestrogen receptor (ESR) gene polymorphisms can predispose to the development of MS in women after menopause.

Study design

The sample consisted of 147 postmenopausal women. In addition to collecting medical history and analyzing body composition using the TANITA scale, patient’s waist size, blood pressure, serum lipids, glucose, insulin, C-reactive protein and adiponectin were measured. The analysis of ESR gene polymorphisms was performed using the Sequenom MassARRAY platform.

Results

Three out of ten analyzed polymorphisms in the ESR1 gene (rs2234693, rs6902771, rs7774230) and one out of eight analyzed polymorphisms in the ESR2 gene (rs3020449) were associated with MS. The ESR1 rs2234693, rs6902771 and rs7774230 polymorphisms were associated with serum concentrations of high-density lipoproteins. The ESR2 rs3020449 polymorphism was associated with serum concentrations of total cholesterol and low-density lipoprotein. Four ESR1 polymorphisms (rs1709183, rs2234693, rs6902771, rs7774230) were associated with total fat tissue content.

Conclusions

Bearing the particular alleles at the ESR gene polymorphisms may impact the development of MS and some of the ESR polymorphisms may influence serum cholesterol concentrations in women after menopause.

Introduction

Metabolic syndrome (MS) is a constellation of risk factors, which, when not treated, leads to the development of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). It is a prevalent condition, which is associated with the growing epidemic of sedentary lifestyle [1]. MS is diagnosed when at least three out of five following risk factors are present: central obesity, elevated serum triglycerides, low HDL cholesterol concentrations, impaired fasting glucose and elevated systolic (SBP) or/and diastolic blood pressure (DBP) [2]. Women after menopause have a higher risk of MS development due to the lack of oestrogens, which have been shown to possess favourable metabolic effects. They prevent visceral fat accumulation and thus improve insulin sensitivity and its metabolic consequences [[3], [4], [5], [6]]. Nowadays, because of the extension of life expectancy, the number of postmenopausal women constantly increases. Therefore, investigating both the environmental and genetic factors predisposing to the development of MS has a great impact on women’s health.

Oestrogens act through two types of nuclear receptors: ERα and ERβ encoded by two different genes (ESR1 located on the chromosome 7 and ESR2 located at the chromosome 14, respectively) [7]. Additionally, there are different genetic variants (polymorphisms) of the ESR1 and ESR2 genes. Previous research has shown associations between having a particular ESR gene polymorphisms and the development of severe diseases in postmenopausal women such as breast, endometrial and ovarian cancer [[8], [9], [10]], T2DM [11], osteoporosis [12] as well as depressive disorders [13].

Therefore the aim of this study was to find out whether bearing the particular alleles at the ESR1 and ESR2 gene polymorphic sites can be associated with the presence of MS in post-menopausal women.