Apolipoprotein A5 gene variants are associated with decreased adiponectin levels and increased arterial stiffness in subjects with low high-density lipoprotein-cholesterol levels.

Abstract

We performed a genome-wide association study to find genetic variants associated with high-density lipoprotein (HDL)-cholesterol levels in a Korean population and verified two apolipoprotein A5 (APOA5) gene variants, rs662799 (-1131T>C) and rs2075291 (c.553G>T), in 612 subjects with low HDL-cholesterol (cases) and 1536 subjects with normal HDL-cholesterol (controls). To explain this association, we compared clinical outcomes according to their genotype in normal (control) and low HDL (case) groups. In both the case and control groups, the rare alleles of rs662799 and rs2075291 were associated with higher triglyceride and lower HDL-cholesterol levels. In the subjects with the rs662799 CC genotype, lower levels of apoA-I and apoA-V and a smaller low-density lipoprotein (LDL) particle size were detected in both the case and control groups. In the case group, APOA5 rs662799 single nucleotide polymorphisms (SNPs) were associated with lower adiponectin and higher brachial-ankle pulse wave velocity (ba-PWV). Our results show that two APOA5 variants, rs662799 (-1131T>C) and rs2075291 (c.553G>T), are associated with HDL-cholesterol levels in a Korean population, and suggest that individuals with an APOA5 rs662799 CC genotype are at higher risk of atherosclerosis, particularly when they have low HDL-cholesterol, and this association is related to adiponectin levels.