ESRα Promoter Methylation May Modify the Association Between Lipid Metabolism and Type 2 Diabetes in Chinese Farmers.

Lihua Liu,Hui Huang,Xing Li,Renjie Sun,Xiangbo Hou,Wenjie Li,Guoyu Zhou,Ling Wang,Zhiyuan Li,Chongjian Wang,Yue Ba

doi:10.3389/fpubh.2021.578134

Abstract

Objective: This study is aimed to explore the potential association among the estrogen receptor alpha (ESRα) promoter methylation, lipid metabolism and the risk of type 2 diabetes mellitus (T2DM).Methods: A total of 1143 rural residents were recruited randomly from Henan Province, China. The circulating methylation levels in ESRα promoter region were determined by quantitative methylation-specific polymerase chain reaction. Serum high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC) and fasting plasma-glucose (FPG) were measured.Results: The ESRα promoter methylation levels were negatively associated with HDL-C levels whether gender stratification was performed (P < 0.05) and positively correlated with LDL-C in men (P < 0.05). Each unit standard deviation (SD) increment in TG was associated with a 43% increase (95% CI: 1.25, 1.64) in the risks of T2DM in all participants, a 36% increase (95% CI: 1.13, 1.64) in the risks of T2DM in men and a 49% increase (95% CI: 1.21, 1.83) in the risks of T2DM in women. Furthermore, each SD increment in HDL-C was associated with a reduction of 25% (OR = 0.75, 95% CI: 0.58, 0.97) in the risks of T2DM in men, and the risk of T2DM in men may be more susceptible to HDL-C than that in women (P for interaction < 0.05). Additionally, we found that the risk of T2DM in participants with lower methylation levels (≤4.07%) were more susceptible to HDL-C (P for interaction < 0.05).Conclusions: These findings suggested that lipid metabolism was associated with ESRα promoter methylation levels and the risk of T2DM. Besides, the levels of ESRα promoter methylation and gender can modify the association of HDL-C and T2DM.

Highlights

Type 2 diabetes mellitus (T2DM) poses a worldwide public health problem with a continuously increasing prevalence in both developing and developed countries [1,2,3]
Diabetic dyslipidemia is mainly a mixed dyslipidemia with higher triglycerides (TG) and low density lipoprotein cholesterol (LDL-C), and lower of high density lipoprotein cholesterol (HDL-C) which can be observed before the onset of diabetes [5,6,7]
As compared to the non-diabetic group, the T2DM group have a lower proportion of men/women, drinking and vegetables intake (≥500 g/day), and a higher proportion of illiteracy and family diabetes history (P < 0.05)

Summary

Introduction

Type 2 diabetes mellitus (T2DM) poses a worldwide public health problem with a continuously increasing prevalence in both developing and developed countries [1,2,3]. Estrogens deficiency can contribute to metabolic dysfunction, and cause obesity and insulin resistance [11, 12]. The estrogens therapy has been revealed to have various beneficial effects by decreasing fasting glucose, increasing insulin sensitivity and secretion and reduce T2DM incidence in postmenopausal women [13, 14]. Ribas et al [16] found that ESRα deficiency can increase fasting insulin levels, impairs glucose tolerance and results in skeletal muscle insulin resistance. Abnormal DNA methylation were found to be associated with lipid metabolism disorders [17, 18]. Whether the alteration of ESRα promoter methylation affects human lipid metabolism and the risk of T2DM has not been explored

Methods

Results

Conclusion