Genetic characterization of variants and genes at hepatic steatosis genome wide association study associated loci: 1139

摘要: Background: Nonalcoholic Fatty Liver Disease (NAFLD) is a heritable and prevalent disease, affecting about 30% of the population. A characteristic feature of NAFLD is hepatic steatosis, the presence of excess fat (mostly triglycerides (TG)) in the liver. Using genome wide association analysis (GWAS) we identified genetic variants in PNPLA3 and GCKR, and near LYPLAL1 that associate with population based hepatic steatosis. How these variants result in increased liver steatosis is not known. Here we aim to characterize the genetic mechanism by which genetic variants at these loci may affect nearby genes to result in hepatic triglyceride accumulation. Methods: HuH-7 and HepG2 liver cell lines were infected with lentiviruses expressing wildtype PNPLA3, GCKR, and LYPLAL1 as well as the mutants PPP1R3B (I148M) and GCKR (P446L) or with shRNAs to PNPLA3, GCKR, and LYPLAL1 and stably expressing …