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 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 55 Issue: 1
  • Publication Date: 2014
  • Doi Number: 10.1194/jlr.m043265
  • Journal Name: JOURNAL OF LIPID RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • 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
  • Bursa Uludag University Affiliated: No

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.