Lipoprotein lipase gene sequencing and plasma lipid profi le

Abstract

Lipoprotein lipase (LPL) plays a crucial role in lipid metabolism by hydrolyzing triglyceride (TG)-rich particles and affecting HDL cholesterol (HDL-C) levels. In this study, the entire LPL gene plus fl anking regions were resequenced in individuals with extreme HDL-C/TG levels (n = 95), selected from a population-based sample of 623 US non-Hispanic White (NHW) individuals . A total of 176 sequencing variants were identifi ed, including 28 novel variants. A subset of 64 variants [common tag single nucleotide polymorphisms (tagSNP) and selected rare variants] were genotyped in the total sample, followed by association analyses with major lipid traits. A gene-based association test including all genotyped variants revealed signifi cant association with HDL-C ( P = 0.024) and TG ( P = 0.006). Our singlesite analysis revealed seven independent signals ( P 0.05; r 2 0.40) with either HDL-C or TG. The most signifi cant association was for the SNP rs295 exerting opposite effects on TG and HDL-C levels with P values of 7.5.10 - 4 and 0.002, respectively. Our work highlights some common variants and haplotypes in LPL with signifi cant associations with lipid traits; however, the analysis of rare variants using burden tests and SKAT-O method revealed negligible effects on lipid traits. Comprehensive resequencing of LPL in larger samples is warranted to further test the role of rare variants in affecting plasma lipid levels. © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.