母孕期应激和NR3C1甲基化与成年期糖脂代谢的相关性

Relationship between maternal stress and NR3C1 methylation during pregnancy and glucose and lipid metabolism in adulthood

目的探讨糖皮质激素受体基因(NR3C1)启动子区DNA甲基化在经历母孕期地震应激人群成年后的代谢改变及其与糖脂代谢水平的相关性。方法于2014年1月至2015年3月选择100例经历母孕期地震应激者作为母孕期地震应激组,于同期选择76例未经历过母孕期地震应激者作为对照组,母孕期地震应激组又根据经历地震时的孕期分为孕早期暴露组(41例)、孕中期暴露组(30例)和孕晚期暴露组(29例)。采用亚硫酸氢盐测序法检测NR3C1启动子区甲基化程度,并收集所有入选者的身高、体重、BMI、血压、空腹血糖、血脂等代谢相关指标。结果母孕期地震应激组的NR3C1启动子区甲基化程度明显高于对照组,差异有统计学意义(P<0.05);亚组比较发现,孕中期暴露组NR3C1启动子区甲基化程度均高于与孕早期及孕晚期暴露组,差异均有统计学意义(P<0.01)。母孕期地震应激组成年期的BMI、总胆固醇高于对照组,差异有统计学意义(P<0.01)。Pearson相关性分析显示,母孕期地震应激组的NR3C1启动子区甲基化程度与其总胆固醇水平呈正相关(r=0.256,P<0.05),而孕中期暴露组则与其甘油三酯及总胆固醇水平呈正相关(r=0.406、0.378,P<0.05)。结论经历母孕期地震应激者较高的NR3C1启动子区甲基化程度与其成年后糖脂代谢水平具有相关性。

Objective To investigate the association between earthquake stress during pregnancy and the methylation status of NR3C1 exon 1F promoter and the influence on glucolipid metabolism in adulthood.Methods From January 2014 to March 2015,100 cases of earthquake stress during pregnancy were selected as the earthquake stress group,and 76 cases without earthquake stress were selected as the control group.According to the pregnant period of earthquake,the pregnant women were divided into early pregnancy exposure group(41 cases),mid pregnancy exposure group(30 cases)and late pregnancy exposure group(29 cases).The methylation degree of NR3C1 promoter region was detected by bisulfite sequencing,and the metabolic indexes such as height,weight,BMI,blood pressure,fasting blood glucose and blood lipid were collected.Rusults NR3C1 methylation level of prenatal earthquake exposure group was significantly higher than that of the control group,and the difference was statistically significant(P<0.05).After comparison of subgroups,the methylation degree of NR3C1 promoter in the second trimester exposure group was higher than that in the early and late pregnancy groups,and the differences were statistically significant(P<0.01).The BMI and total cholesterol of adult in earthquake stress group were higher than those in control group,the difference was statistically significant(P<0.01).Pearson correlation analysis showed that the methylation degree of NR3C1 promoter region was positively correlated with total cholesterol(r=0.256,P<0.05)in maternal earthquake stress group,while it was positively correlated with triglyceride and total cholesterol in the second trimester exposure group(r=0.406,0.378,P<0.05).Conclusions There was significant association between increased NR3C1 exon 1F methylation and glucolipid metabolism in adulthood with prenatal earthquake stress.