糖尿病分子生物学和遗传学

　　【摘要】 目的 探讨肿瘤坏死因子α(TNF-α)基因启动子区甲基化及mRNA的表达与新疆维吾尔族肥胖及T2DM的相关性。 方法 选取腹部择期手术的维吾尔族患者124例，分为对照组(Con)组50例、肥胖(Ob)组48例，以及T2DM组26例。术时取网膜脂肪组织，采用变性高效液相色谱法(DHPLC)对TNF-α基因启动子区DNA甲基化进行检测。RT-PCR检测TNF-α mRNA表达情况。 结果 TNF-α基因启动子区DNA甲基化阳性率在NC组(70.0%)、Ob组(47.9%)及T2DM组(26.9%)逐渐降低(P<0.01)。NC组TNF-α mRNA相对拷贝数低于Ob组及T2DM组(P<0.05)。TNF-α基因启动子区DNA甲基化阳性组mRNA相对拷贝数(0.0542)低于阴性组(0.1988)(P<0.01)。 结论 腹腔脂肪组织TNF-α基因启动子区DNA甲基化抑制其mRNA表达可能是新疆维吾尔族肥胖及T2DM发生的危险因素。

　　【关键词】糖尿病，2型;肥胖;肿瘤坏死因子α;甲基化

　　【Abstract】 Objective To investigate the relationship between type 2 diabetes mellitus (T2DM), obesity and mRNA expression and promoter methylation of tumor necrosis factor-α(TNF-α) gene in abdominal adipose tissues of Xinjiang Uygur population. Method A total of 124 patients undergoing time selecting abdominal operation were enrolled in this study and divided into three groups : normal control (NC) group (n=50), obesity(Ob) group (n=50), and T2DM group (n=26). The intra-abdominal adipose tissue was collected during operation.The status of TNF-α gene promoter region DNA methylation was detected by DHPLC and the mRNA expression of TNF-α was detected by RT-PCR. Result The methylation positive rate of TNF-α was significantly decreased in NC, Ob and T2DM group ( 70.0%, 47.8%, and 26.9, respectively,P<0.01). The TNF-α mRNA expression was significantly lower in NC group than in Ob and T2DM groups (P<0.05). The TNF-α mRNA expression in promoter methylation of tumor necrosis factor-α(TNF-α) positive group was significantly lower than negative group(P<0.01). Conclusion In intra-abdominal adipose tissue, TNF-α mRNA expression was suppressed by promoter region DNA methylation status, which could be a risk factor for the development of obesity and T2DM in Uygur people.

　　【Key words】Diabetes mullitus，type2;Obesity; Tumor necrosis factor ;Methylation