Lipoprotein lipase gene sequencing and plasma lipid profile


PİRİM D. , Wang X., Radwan Z. H. , Niemsiri V., Hokanson J. E. , Hamman R. F. , ...More

JOURNAL OF LIPID RESEARCH, vol.55, no.1, pp.85-93, 2014 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 55 Issue: 1
  • Publication Date: 2014
  • Doi Number: 10.1194/jlr.m043265
  • Title of Journal : JOURNAL OF LIPID RESEARCH
  • Page Numbers: pp.85-93
  • Keywords: triglycerides, lipid metabolism, rare variants, candidate gene, genotyping, genetic association, CORONARY-ARTERY-DISEASE, GENOME-WIDE ASSOCIATION, HDL-CHOLESTEROL LEVELS, RARE VARIANTS, HEART-DISEASE, CARDIOVASCULAR-DISEASE, SERUM-LIPOPROTEIN, RISK, POLYMORPHISMS, POPULATION

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 flanking 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 identified, 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 significant association with HDL-C (P = 0.024) and TG (P = 0.006). Our single-site analysis revealed seven independent signals (P < 0.05; r(2) < 0.40) with either HDL-C or TG. The most significant 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 significant 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.