Pleiotropic Effects of Variants on Lipid Profiles, Metabolic Syndrome, and the Risk of Diabetes Mellitus

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Dec 11

PMID 36499290

Authors

Shih-Jung Jang

Wei-Lun Tuan

Lung-An Hsu

Leay-Kiaw Er

Ming-Sheng Teng

Semon Wu

Yu-Lin Ko

Affiliations

Soon will be listed here.

Abstract

Apolipoprotein B (ApoB) plays a crucial role in lipid and lipoprotein metabolism. The effects of locus variants on lipid profiles, metabolic syndrome, and the risk of diabetes mellitus (DM) in Asian populations are unclear. We included 1478 Taiwan Biobank participants with whole-genome sequence (WGS) data and 115,088 TWB participants with Axiom genome-wide CHB array data and subjected them to genotype-phenotype analyses using locus variants. Five nonsynonymous mutations, including Asian-specific rs144467873 and rs13306194 variants, were selected from participants with the WGS data. Using a combination of regional association studies, a linkage disequilibrium map, and multivariate analysis, we revealed that the locus variants rs144467873, rs13306194, and rs1367117 were independently associated with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL) cholesterol levels; rs1318006 was associated with HDL cholesterol levels; rs13306194 and rs35131127 were associated with serum triglyceride levels; rs144467873, rs13306194, rs56213756, and rs679899 were associated with remnant cholesterol levels; and rs144467873 and rs4665709 were associated with metabolic syndrome. Mendelian randomization (MR) analyses conducted using weighted genetic risk scores from three or two LDL-cholesterol-level-associated variants revealed significant association with prevalent DM ( = 0.0029 and 8.2 × 10, respectively), which became insignificant after adjustment for LDL-C levels. In conclusion, these results indicate that common and rare variants are independently associated with various lipid levels and metabolic syndrome in Taiwanese individuals. MR analyses supported variants associated with the risk of DM through their associations with LDL cholesterol levels.

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