非酒精性脂肪肝过氧化物酶体增殖物激活受体α基因甲基化水平与高脂血症的相关性研究

STUDY ON THE CORRELATION BETWEEN UP-REGULATED EXPRESSION OF THE METHYLATION LEVEL OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA(PPARα)-GENE AND HYPERLIPIDEMIA IN NON-ALCOHOLIC FATTY LIVER PATIENTS

目的检测非酒精性脂肪肝(NAFLD)患者外周血过氧化物酶体增殖物激活受体(PPARα)基因启动子的甲基化水平与高脂血症的相关性。方法病例对照研究。收集对照组(N)60例、高脂血症组(NT)62例和NAFLD合并高脂血症组(TT)65例的临床资料,测定血清中总胆固醇(TCH)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)的含量。使用以甲基化特异性聚合酶链反应(MSP)法,检测外周血PPARα基因启动子甲基化水平。并分析其与血脂水平等临床资料的关系。结果实验三组性别和年龄相匹配。NT组和TT组TCH和TG均显著高于N组,TT组TG较NT组明显上升,而两组TCH含量无明显差异;TT组PPARα基因启动子甲基化率明显高于N组及NT组(X^2=5.05、4.13,P均<0.05),后两组无明显差异(P>0.05);该基因的甲基化率与TG有相关性(t=2.38,P<0.05),而与患者年龄、身高、体质量、体重指数、TCH、HDL-C和LDL-C无相关性(t=1.04、1.12、1.56、0.08、1.93、0.98、0.72,均P>0.05)。结论 NAFLD患者PPARα基因启动子的甲基化率明显增加,与高甘油三酯血症呈正相关,是NAFLD的重要发病机制之一。

Objective To determine the methylation level of peroxisome proliferator-activated receptor （PPAR）-ct gene promoter in peripheral blood of patients with non-alcoholic fatty liver disease （NAFLD）, and investigate the correlation between the methylation level of PPAR-a gene promoter and hyperlipidemia. Methods The serum levels of total cholesterol （TCH）, triglycerides （TG）, high density lipoprotein-cholesterol （HDL-C） and low density lipoproteincholesterol（LDH-C） were assessed in 62 hyperlipidemia patients （NT group）, 65 NAFLD with hyperlipidemia patients （TT group）, and 60 healthy controls （N group）. Methylation-specific PCR （MSP） was used to characterize the methylation level of PPARct gene promoter. Results were analyzed for potential correlations between biochemistry data and clinical data. Results there were no difference in the mean age and gender among the three groups. Levels of TCH and TG were higher in NT group and TT group compared with those in N group. Levels of TG in TT group were higher than NT group. The methylation level of PPARu gene promoter in TT group was significantly higher than in N and NT group （Z2 =5.05, 4.13, P〈0.05）. However, there was no significant difference between N and NT groups （P〉0.05）. There was a positive correlation between TG and methylation level of PPAR-ct gene promoter （t = 2.38, P 〈0.05）, but not age, 1.56, 0.08, 1.93, 0.98, 0.72, P〉0.05）. Conclusion height, weight, BMI, TCH, HDL-CorLDL-C（t=1.04, 1.12, The methylation level of PPARa gene promoter was significantly increased and positively correlated with hypertriglyceridemia in NAFLD patients, which may contribute to the NAFLD development and progression.