FOS样抗原2 mRNA及DNA甲基化在新疆维吾尔族2型糖尿病患者中的表达分析

Expression and analysis of FOSL2 mRNA and its DNA methylation in patients with type 2 diabetes mellitus of Xinjiang Uygur nationality

目的分析FOS样抗原2(FOSL2)mRNA及DNA甲基化在新疆维吾尔族T2DM患者中的表达。方法选取2015年1月至2016年1月于莎车县人民医院内分泌科就诊的维吾尔族人群100例,分为糖耐量正常(NGT)组和T2DM组,每组各50例。测定HbA1c、FPG、TG、TC等生化指标,采用RT-PCR、MALDI-TOF-MS检测外周血白细胞FOSL2 mRNA表达及DNA甲基化水平,多元线性回归分析影响因素。结果与NGT组比较,T2DM组BMI、HbA1c、FPG、TG、TC、LDL-C升高(P<0.05或P<0.01),HDL-C、FOSL2 mRNA表达降低(P<0.05或P<0.01)。T2DM组FOSL2基因有7个CPG单位的甲基化水平升高(P<0.05或P<0.01)。相关分析显示,T2DM组FOSL2基因DNA甲基化水平与mRNA表达呈负相关(r=-0.39,P<0.05)。多元线性回归结果显示,BMI、HbA1c是新疆维吾尔族T2DM患者FOSL2基因DNA甲基化高表达的危险因素(P<0.05)。结论新疆维吾尔族T2DM患者存在肥胖、血脂代谢紊乱等,通过FOSL2基因DNA高甲基化下调其mRNA表达,可能在T2DM发病中起作用。

Objective To analyze the expression of FOSL2 mRNA and its DNA methylation in Xinjiang Uygur T2DM.Methods From January 2015 to January 2016,100 Uygur population in the Department of Endocrinology of Shache County People’s Hospital were selected and divided into normal glucose tolerance(NGT,n=50)group and T2DM group(n=50).Biochemical indexes such as HbA1c,FPG,TG and TC were measured.FOSL2 mRNA expression and DNA methylation level were detected by RT-PCR and MALDI-TOF-MS.The influencing factors were analyzed by multiple linear regression.Results Compared with NGT group,BMI,HbA1c,FPG,TG,TC and LDL-C increased in T2DM group(P<0.05 or P<0.01),and the expression of HDL-C and FOSL2 mRNA decreased(P<0.05 or P<0.01).The methylation level of 7 Cp G units in FOSL2 gene in T2DM group was increased(P<0.05 or P<0.01).The level of DNA methylation of FOSL2 gene was negatively correlated with mRNA expression in T2DM group(r=-0.39,P<0.05).The results of multiple linear regression showed that BMI and HbA1c were the risk factors for the high expression of FOSL2 gene DNA methylation in T2DM patients of Xinjiang Uygur(P<0.05).Conclusion Obesity and dyslipidemia are common in T2DM patients in Xinjiang Uygur.Down regulation of FOSL2 mRNA expression through DNA hypermethylation of FOSL2 gene may play a role in the pathogenesis of T2DM.