Department of Environment Health & Environment and Health Innovation Team, School of Public Health, Zhengzhou University, Zhengzhou, China.
Yellow River Institute for Ecological Protection & Regional Coordinated Development, Zhengzhou University, Zhengzhou, China.
Front Public Health. 2021 Mar 4;9:578134. doi: 10.3389/fpubh.2021.578134. eCollection 2021.
This study is aimed to explore the potential association among the estrogen receptor alpha (α) promoter methylation, lipid metabolism and the risk of type 2 diabetes mellitus (T2DM). A total of 1143 rural residents were recruited randomly from Henan Province, China. The circulating methylation levels in 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. The α promoter methylation levels were negatively associated with HDL-C levels whether gender stratification was performed ( < 0.05) and positively correlated with LDL-C in men ( < 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% : 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 ( 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 ( for interaction < 0.05). These findings suggested that lipid metabolism was associated with α promoter methylation levels and the risk of T2DM. Besides, the levels of α promoter methylation and gender can modify the association of HDL-C and T2DM.
这项研究旨在探讨雌激素受体α（α）启动子甲基化、脂代谢与 2 型糖尿病（T2DM）风险之间的潜在关联。本研究共招募了 1143 名来自中国河南省的农村居民。采用定量甲基化特异性聚合酶链反应（qMSP）测定α启动子区域的循环甲基化水平。检测血清高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）、总胆固醇（TC）和空腹血糖（FPG）。
无论进行性别分层与否（<0.05），α 启动子甲基化水平与 HDL-C 水平呈负相关，且与男性 LDL-C 呈正相关（<0.05）。所有参与者中，TG 每增加一个标准差（SD），T2DM 的风险增加 43%（95%CI：1.25，1.64）；男性中，T2DM 的风险增加 36%（95%CI：1.13，1.64）；女性中，T2DM 的风险增加 49%（95%CI：1.21，1.83）。此外，HDL-C 每增加一个 SD，男性 T2DM 的风险降低 25%（OR=0.75，95%CI：0.58，0.97），且男性 T2DM 的风险比女性更易受 HDL-C 影响（交互作用<0.05）。此外，我们发现较低甲基化水平（≤4.07%）的参与者发生 T2DM 的风险对 HDL-C 更为敏感（交互作用<0.05）。
这些发现表明，脂代谢与α 启动子甲基化水平和 T2DM 风险有关。此外，α 启动子甲基化水平和性别可以调节 HDL-C 与 T2DM 的关联。
