Chen Lizhen, Du Shuixian, Lu Linlin, Lin Zhonghua, Jin Wenwen, Hu Doudou, Jiang Xiangjun, Xin Yongning, Xuan Shiying
College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, Shandong, China.
Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong, China.
Oncotarget. 2017 Jun 14;8(43):74209-74216. doi: 10.18632/oncotarget.18474. eCollection 2017 Sep 26.
There is a genetic susceptibility for nonalcoholic fatty liver disease (NAFLD). To examine the role of genetic factors in the disease, a Bayesian analysis was performed to model gene relationships in NAFLD pathogenesis. The Bayesian analysis indicated a potential gene interaction between the and genes. Next, to explore the underlying mechanism at the cellular level, we evaluated the additive effects between the and polymorphisms on lipid metabolism. Hepa 1-6 cells were transfected with a control vector or with overexpression vectors for TM6SF2/PNPLA3-wild type, TM6SF2-mutant type, PNPLA3-mutant type, or TM6SF2/PNPLA3-mutant type. Commercial kits were used to measure triglyceride and total cholesterol levels in each of the five groups. The mRNA and protein expression levels of sterol regulatory element-binding transcription factor 1c and fatty acid synthase were analyzed using real-time PCR and western blotting. The triglyceride and total cholesterol contents were significantly different among the groups. The triglyceride and total cholesterol contents and the sterol regulatory element-binding transcription factor 1c and fatty acid synthase mRNA and protein expression levels were significantly higher in the TM6SF2/PNPLA3-mutant type group than in the TM6SF2-mutant type group or the PNPLA3-mutant type group. The and polymorphisms may have additive effects on lipid metabolism by increasing the expression of sterol regulatory element-binding transcription factor 1c and fatty acid synthase.
非酒精性脂肪性肝病（NAFLD）存在遗传易感性。为了研究遗传因素在该疾病中的作用，进行了贝叶斯分析以建立NAFLD发病机制中的基因关系模型。贝叶斯分析表明[未提及的两个基因]之间存在潜在的基因相互作用。接下来，为了在细胞水平探索潜在机制，我们评估了[未提及的两个基因]多态性对脂质代谢的累加效应。将Hepa 1-6细胞用对照载体或TM6SF2/PNPLA3野生型、TM6SF2突变型、PNPLA3突变型或TM6SF2/PNPLA3突变型的过表达载体进行转染。使用商业试剂盒测量五组中每组的甘油三酯和总胆固醇水平。使用实时PCR和蛋白质印迹法分析固醇调节元件结合转录因子1c和脂肪酸合酶的mRNA和蛋白质表达水平。各组之间甘油三酯和总胆固醇含量存在显著差异。TM6SF2/PNPLA3突变型组中的甘油三酯和总胆固醇含量以及固醇调节元件结合转录因子1c和脂肪酸合酶的mRNA和蛋白质表达水平显著高于TM6SF2突变型组或PNPLA3突变型组。[未提及的两个基因]多态性可能通过增加固醇调节元件结合转录因子1c和脂肪酸合酶的表达对脂质代谢产生累加效应。
