478-P: GALNT2 Variant Associates with Increased ANGPTL3 Circulation Level and Obesity

Abstract

Background: Polypeptide N-Acetylgalactosaminyltransferase 2 (GALNT2) gene has been associated with serum lipid levels, insulin resistance, and adipogenesis. One of its variants, rs4846914 has been shown to associate with Triglycerides and HDL levels in global genome-wide association studies. ANGPTL proteins have emerged as important regulators of lipid metabolism through its regulation of lipoprotein lipase activity. In this study we aimed to evaluate the association between GALNT2 variant with plasma level of ANGPTL3, 8 and apolipoproteins in individuals of Arab ethnicity. Methods: GALNT2 rs4846914 variant was genotyped in a cohort of 278 Arab individuals from Kuwait. Plasma levels of ANGPTL3 and 8 were measured by ELISA. Apolipoproteins were measured by Luminex multiplexing assay. Significance of association signals was assessed using Bonferroni-corrected P-values. Results: The GALNT2 rs4846914_G allele was associated with increased ANGPTL3 but not ANGPTL8 plasma levels. It was associated with obesity status with an odds ratio of 1.45 (CI:1.024-2.055) (P-value =0.036) . It also associated with increased levels of ApoC1 (P-values ≤0.006) and lower levels of HDL (P-values ≤0.05) . Levels of HDL were found to be mediated by interactions between genotypes (AG+GG) at rs4846914 and measures of percentage body fat (PBF) , apolipoproteins A1a, C1 and B48. Conclusions: Association between GALNT2 variant and lipid metabolism could be mediated through the increased ANGPTL3 protein level. Disclosure A.T.Thangavel: None. M.Abu-farha: None. P.Hebbar: None. M.G.Qaddoumi: None. F.Almulla: None. J.Abubaker: None.