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

• Published in: Circulation Vol. 146; no. Suppl_1; p. A11228
• Main Authors: Ikezaki, Hiroaki, Schaefer, Ernst J, Murata, Masayuki, Shimono, Nobuyuki
• Format: Journal Article
• Language: English; Japanese
• Published: Ovid Technologies (Wolters Kluwer Health) 08.11.2022; Lippincott Williams & Wilkins
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.146.suppl_1.11228

IntroductionNonalcoholic 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. HypothesisWe hypothesized that NAFLD genetic risk alleles are associated with the progression of atherosclerosis. MethodsA 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. ResultsBoth 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. ConclusionsA NCAN variant, one of the NAFLD risk SNPs, was associated with the development of plaque independent of lipoproteins alterations among healthy Japanese participants.