Abstract 11228: Association Between Nonalcoholic Fatty Liver Disease Risk Alleles and Atherosclerosis

Abstract

Introduction: Nonalcoholic fatty liver disease (NAFLD) risk alleles are associated with lipid metabolisms. However, the association between those variants and atherosclerosis has not yet been fully evaluated. Hypothesis: We hypothesized that NAFLD genetic risk alleles are associated with the progression of atherosclerosis. Methods: A total of 1,050 Japanese men and women (median age 55 years and median body mass index 22.9 kg/m2) free of cardiovascular disease, dyslipidemia, hypertension, and diabetes 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, LDL-triglycerides, high-density lipoprotein cholesterol (HDL-C), HDL3-C, triglycerides, remnant-like particle cholesterol, lipoprotein(a), and adiponectin were also measured. At both baseline and after a five-year follow-up, carotid intima-media thickness (cIMT) was assessed. Atherosclerosis was defined as cIMT more than 1.1mm or the presence of a plaque. Univariate and multivariate analyses and chi-square and Fisher’s exact tests were performed to examine the associations between NAFLD risk SNPs, lipoproteins, and progression of atherosclerosis. Results: Both median and maximum cIMT of total participants did not differ between baseline and after a five-year follow-up. Among participants without atherosclerosis at baseline, the rate of plaque development was 13.8% (121/880) with the major allele (CC) of NCAN being significantly higher than other alleles. Variants of NCAN were associated with the development of plaque ( P = 0.04, Fisher’s exact test). Variants of PNPLA3 , TM6SF2 , GCKR , and NCAN were not associated with changes in lipoproteins. Conclusions: A NCAN variant, one of the NAFLD risk SNPs, was associated with the development of plaque independent of lipoproteins alterations among healthy Japanese participants.