The additive effects of the TM6SF2 E167K and PNPLA3 I148M polymorphisms on lipid metabolism
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Lizhen Chen1,2, Shuixian Du3, Linlin Lu4, Zhonghua Lin2, Wenwen Jin2, Doudou Hu2, Xiangjun Jiang2, Yongning Xin2 and Shiying Xuan1,2
1College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, Shandong, China
2Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, Shandong, China
3Medical College, Qingdao University, Qingdao, Shandong, China
4Central Laboratories, Qingdao Municipal Hospital, Qingdao, Shandong, China
Yongning Xin, email: email@example.com
Shiying Xuan, email: firstname.lastname@example.org
Keywords: nonalcoholic fatty liver disease, additive effect, TM6SF2, PNPLA3, bayesian network
Received: January 10, 2017 Accepted: March 31, 2017 Published: June 14, 2017
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 TM6SF2 and PNPLA3 genes. Next, to explore the underlying mechanism at the cellular level, we evaluated the additive effects between the TM6SF2 E167K and PNPLA3 I148M 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 TM6SF2 E167K and PNPLA3 I148M polymorphisms may have additive effects on lipid metabolism by increasing the expression of sterol regulatory element-binding transcription factor 1c and fatty acid synthase.
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