title: Lipoprotein lipase gene sequencing and plasma lipid profile.
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; r² < 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.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; and.
authors.forename: Dilek
authors.initials: D
authors.lastname: Pirim
authors.forename: Xingbin
authors.initials: X
authors.lastname: Wang
authors.forename: Zaheda H
authors.initials: ZH
authors.lastname: Radwan
authors.forename: Vipavee
authors.initials: V
authors.lastname: Niemsiri
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: Richard F
authors.initials: RF
authors.lastname: Hamman
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
authors.forename: F Yesim
authors.initials: FY
authors.lastname: Demirci
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood*
chemical_list: D008076:Cholesterol, HDL; D014280:Triglycerides; D008071:Lipoprotein Lipase
keywords: candidate gene; genetic association; genotyping; lipid metabolism; rare variants; triglycerides