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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 investigate the relationship between hypermethylation of hyperlipidemia and methylation of peroxisome proliferator activated receptor (PPARα) promoter in peripheral blood of patients with nonalcoholic fatty liver disease (NAFLD). Methods Case-control study. The clinical data of 60 cases of control group (N), 62 cases of hyperlipidemia group (NT) and 65 cases of NAFLD combined with hyperlipidemia group (TT) were collected for determination of serum total cholesterol (TCH), triglyceride ), High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) content. The methylation level of PPARα gene promoter in peripheral blood was detected by methylation-specific polymerase chain reaction (MSP). And analyze the relationship with the clinical data such as blood lipid level. Results Three groups were matched by sex and age. TCH and TG in NT group and TT group were significantly higher than those in N group, while TG in TT group was significantly higher than that in NT group, while there was no significant difference in TCH content between two groups. The methylation rate of PPARα gene promoter in TT group was significantly higher than that in N group and NT group There was no significant difference between the two groups (P> 0.05). The methylation rate of this gene was correlated with TG (t = 2.38, P <0.05) But no correlation with patient age, height, body mass, body mass index, TCH, HDL-C and LDL-C (t = 1.04,1.12,1.56,0.08,1.93,0.98,0.72, all P> 0.05). Conclusions The methylation rate of PPARα gene promoter in NAFLD patients is significantly increased, which is positively correlated with hypertriglyceridemia and is one of the important pathogenesis of NAFLD.