新疆维吾尔族2型糖尿病患者血液白细胞中FOSL2mRNA表达水平及其临床意义

目的: 比较FOS样抗原2(FOSL2)mRNA在新疆维吾尔族2型糖尿病(T2DM)患者及正常糖代谢(NGT)人群中的表达水平,并分析其表达与研究对象临床生化指标的相关性。方法: 收集新疆喀什地区维吾尔族T2DM(T2DM组)患者50例和NGT者(NGT组)50人,测量并记录其一般临床指标,如性别、年龄、脉搏、收缩压(SBP)、舒张压(DBP)、腰臀比(WHR)、体质量指数(BMI),记录T2DM病程(根据WHO糖尿病诊断标准确诊),采集血液标本。生化分析仪测定2组研究对象的空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)等糖脂代谢指标;全自动电化学发光分析仪及配套试剂测定空腹胰岛素(FINS)水平;高压液相色谱法(HPLC)测定糖化血红蛋白(HbAlc)水平;RT-PCR法测定血液中FOSL2mRNA表达水平。结果: 与NGT组比较,T2DM组患者的BMI(t=-4.62,P=0.00)、FPG(t=-9.56,P=0.00)、HbAlc(t=-7.83,P=0.00)、TC(t=-7.86,P=0.00)、TG(t=-3.89,P=0.00)和LDL-C(t=-2.41,P=0.01)水平升高。而HDL-C水平和FOSL2mRNA表达水平(t=-2.58,P=0.01;t=-12.174,P=0.000)降低。与NGT组比较,T2DM组患者的FINS(t=-2.42,P=0.02)、胰岛素抵抗指数(HOMA-IR)(t=-6.46,P=0.00)、胰岛β细胞功能指数(In-HOMA-β)(t=-5.58,P=0.00)升高,胰岛素敏感指数(In-ISI)(t=6.80,P=0.00)降低。T2DM患者白细胞中FOSL2mRNA表达水平与WHR(r=-0.415,P=0.008)、FPG(r=-0.620,P=0.000)、HbAlc(r=-0.681,P=0.000)、HOMA-IR(r=-0.504,P=0.001)、TC(r=-0.582,P=0.000)、TG(r=-0.342,P=0.031)和HDL-C(r=-0.323,P=0.042)、T2DM病程(r=-0.733,P=0.000)呈负相关关系,与In-HOMA-β(r=0.638,P=0.000)呈正相关关系。回归分析,T2DM病程(β=-0.056,P=0.002)、In-HOMA-β(β=0.342,P=0.001)和TC(β=-0.219,P=0.003)为FOSL2基因表达水平的影响因素。结论: FOSL2mRNA表达水平下调参与新疆维吾尔族人群胰岛素抵抗和T2DM发生发展,TC是维吾尔族T2DM患者FOSL2基因表达水平下调的重要影响因素。

Expression level of FOSL2 mRNA in blood leukocytes of type 2 diabetes mellitus patients in Uygurs in Xinjiang and its clinical significance

Objective: To compare the expression levels of Fos-like antigen 2 (FOSL2) mRNA of the patients with type 2 diabetes mellitus(T2DM) and the subjects with nomal glucose tolerance (NGT) in Uygurs in Xinjiang,and to analyze the correlation between the FOSL2 mRNA expression and the clinical and biochemical indicators of the subjects. Methods: A total of 50 Uygrus adult patients with T2DM(T2DMgroup) and 50 cases of NGT (NGT group) were collected respectively in Kashi area in Xinjiang.The general clinical indicators,such as gender,age,pulse,systolic blood pressure(SBP),diastolic blood pressure(DBP),WHR,BMI, and T2DM disease course identified by the diagnostic criteria of WHO were recorded,and the blood samples were collected at the same time.The metabolic markers such as fasting blood glucose(FPG) total cholesterol(TC),TG,LDL-C and HDL-C were measured by clinical chemistry analyzer;the level of fasting serum insulin (FINS) was measured by automatic chemiluminescence analyzer;the level of HbAlc was mesured by high pressure liquid chromatography(HPLC);the expression levels of FOSL2 mRNA in leukocytes of the subjects were examined by RT-PCR method. Results: Compared with NGT group,the BMI(t=-4.62,P=0.00),level of FPG(t=-9.56,P=0.00),HbA1c(t=-7.83,P =0.00),TC(t=-7.86,P =0.00),TG(t=-3.89,P=0.00),and LDL-C(t=-2.41,P =0.01) were increased;however,the level of HDL-C(t=-2.58,P=0.01)and FOSL2 mRNA expression level(t=-12.174,P =0.00)in leukocytes of the patients in T2DM group were decreased. Compared with NGT group,the FINS(t=-2.42,P=0.02),homeostasis model assessment of insulin resistance(HOMA-IR) (t=-6.46,P=0.00),nataral logarithm homeostasis model assessment of insulin β-cell function(In-HOMA-β) (t=5.58,P=0.00) of the patients in T2DM group were increased ,and the nataral logarithm insulin sensitivity index(In-ISI) (t=6.80,P=0.00) was decreased. WHR(r=-0.415,P=0.008),and the levels of FPG(r=-0.620,P=0.000),HbAlc(r=-0.681,P=0.000),HOMA-IR(r=-0.504,P=0.001),TC(r=-0.582,P=0.000),TG(r=-0.342,P=0.031),T2DM disease course (r=-0.733,P=0.000) and HDL-C(r=-0.323,P=0.042)were negatively correlated with the expression level of FOSL2 mRNA in leukocytes of the T2DM patients. The level of In-HOMA-β(r=0.638,P=0.000) showed a positive correlation with the expression level of FOSL2 mRNA. The results of regression analysis showed that T2DM disease course(β=-0.056,P=0.002),In-HOMA-β(β=0.342,P=0.001),and TC(β=0.219,P=0.003)were the influencing factors of the level of FOSL2 mRNA in the T2DM patients. Conclusion: The down-regulation of expression level of FOSL2 mRNA may be involved in the occurrence and development of insulin resistance and T2DM in Uygurs in Xinjiang.TC is an important factor of the down-regulation of expression level of FOSL2 mRNA in the Uggurs patients with T2DM.