Abstract P181: Association Between Non-Alcoholic Fatty Liver Disease Risk SNP Variants and Lipid Metabolism

Abstract

Introduction: The impact of non-alcoholic fatty liver disease (NAFLD) risk SNP variants on ipid metabolism in the general population has yet to be determined. We aimed to assess this association using a large prospective cohort study. Methods: A total of 1488 Japanese men and women (median age 62 years and median body mass index 24.7 kg/m2) free of cardiovascular disease were studied. Among NAFLD risk SNPs, variants of patatin-like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), glucokinase regulator (GCKR), and neurocan (NCAN) were assessed. Plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL3-C, triglycerides (TG), lipoprotein(a), and adiponectin were measured at both baseline and after a five-year follow-up. Univariate and multivariate analyses, Kruskal-Wallis, Wilcoxon’s rank sum, and paired t-tests were performed to examine the associations between NAFLD risk SNPs and lipoproteins. Results: All of the measured lipoproteins increased significantly over the 5 years. The TM6SF2 variant did not affect lipoproteins at baseline. However, after 5 years, the non-major allele group had significantly lower HDL-C and HDL3-C and significantly higher LDL-C, sdLDL-C, and LDL-TG than the major allele group. For the GCKR variant, TG, LDL-C, sdLDL-C, and LDL-TG were significantly higher in the non-major allele group at baseline; LDL-C, sdLDL-C, and LDL-TG were still significantly higher in the non-major allele group at 5 years than the CC group. The PNPLA3 and NCAN variants did not affect lipoproteins in this study. Conclusions: NAFLD risk SNP variants might influence atherogenic lipoprotein metabolism.