腹部脂肪组织APN基因DNA甲基化及mRNA表达与维吾尔族T2DM的相关性

为探讨APN基因启动子区DNA甲基化及mRNA表达与新疆维吾尔族T2DM发生、发展的相关性,文章选择新疆维吾尔族正常个体50例、肥胖个体48例、肥胖伴T2DM个体26例,收集腹部网膜脂肪组织,利用变性高效液相色谱技术检测APN基因启动子区DNA甲基化情况,应用Real-time PCR方法检测APN 基因mRNA表达情况。结果显示,APN基因启动子区DNA甲基化阳性率在正常对照(34%)、肥胖(47.9%)及T2DM组(65.4%)逐渐增加,差异具有统计学意义(P<0.05)。Real-time PCR结果显示,正常对照组APN mRNA相对拷贝数(0.7162)显著高于肥胖(0.4244)及T2DM组(0.4093),差异具有统计学意义(P<0.05)。非T2DM个体相关性分析提示,APN mRNA相对拷贝数与空腹血清葡萄糖(Fasting plasma glucose, FPG)、糖化血红蛋白(Glycosylated hemoglobin, HbA₁c)、甘油三酯(Triglyceride, TG)水平显著负相关(P<0.05)。APN基因启动子区DNA甲基化与其mRNA表达负相关,甲基化阳性组相对拷贝数(0.2700)显著低于阴性组(0.7870),差异具有统计学意义(P<0.01)。以上结果提示,APN基因启动子区DNA甲基化通过抑制其 mRNA表达导致糖脂代谢紊乱,可能参与了新疆维吾尔族肥胖及T2DM的发生、发展过程。

Correlation between type 2 diabetes and DNA methylation and mRNA expression of APN in abdominal adipose tissues in Xinjiang Uygur population

To investigate the relationship between type 2 diabetes mellitus (T2DM) onset and development and mRNA expression and promoter methylation of adiponectin (APN) gene in abdominal adipose tissues of Xinjiang Uygur population, abdominal adipose tissues of omentum were collected and divided into control, obesity and T2DM groups. The status of APN promoter methylation was detected by denaturing high performance liquid chromatography (DHPLC), while the mRNA expression level of APN was detected by RT-PCR. Results show that methylation positive rate of APN was at the lowest level in control, middel in obesity and highest in T2DM groups, and the differences are statistically significant. Comparing the APN mRNA relative copy number of adipose tissue in each group, we found that the relative copy number of APN in control group is significantly higher than that of obesity and T2DM groups. There is a negative correlation between the mRNA expression level of APN in abdominal adipose tissue and fasting plasma glucose (FPG), glycosylated hemoglobin (HbA₁c) and triglyceride (TG) level. There is a negative correlation in DNA promoter methylation and mRNA expression of APN gene. Relative copy number of APN in DNA methylation positive group is significantly lower than that of the negative group. In conclusion, increased APN promoter methylation results in decreased mRNA expression, which induces glucose and lipid metabolic disorder, thus contributing to the initiation and development of T2DM in Xinjiang Uygur population.