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Background A part of nonalcoholic fatty liver disease (NAFLD) develops nonalcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma. Metabolic syndrome is involved in their development, and hepatic fibrosis plays an important role in their pathogenesis. Patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene encode proteins on hepatic lipid metabolism regulation, and PNPLA3 gene polymorphism is associated with the development and progression of NAFLD. To investigate the gene and environmental factors, and their interaction for liver fibrosis, we conducted a prospective study among Japanese general population with NAFLD. Methods The subjects were 295 general residents who participated as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study in Kagoshima, Japan, and were followed for 5 years. NAFLD was defined as fatty liver using abdominal ultrasonography. PNPLA3 C/G polymorphism (rs738409) was analysed using TaqMan PCR. Hepatic fibrosis was defined using FIB 4 index (≥1.3). Logistic regression model was used to estimate the odds ratios (ORs) after adjusted for confounding factors. Results Mean age was 55.1 years and liver fibrosis was observed at 73.2% among NAFLD subjects. No environmental factors were associated with liver fibrosis, and PNPLA3 GG genotype was not associated with liver fibrosis, too. However, the ORs of CC &amp; CG, and GG genotypes for dyslipidemia was respectively 0.45 (0.19-1.04) and 11.9 (1.81-78.4), and their interaction was significant (p = 0.01). Conclusions The interaction between PNPLA3 GG gene polymorphism and dyslipidemia for liver fibrosis was observed. Key messages Genetic susceptibility with dyslipidemia may be involved in liver fibrosis of NAFLD.

695Gene and environmental factors for liver fibrosis among Japanese general population with NAFLD