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Objective:  This study is aimed to explore the potential association among the estrogen receptor alpha ( ESR α) 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  ESR α 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  ESR α 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  ESR α promoter methylation levels and the risk of T2DM. Besides, the levels of  ESR α promoter methylation and gender can modify the association of HDL-C and T2DM.

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