Lipoprotein lipase gene sequencing and plasma lipid profile

被引:18
作者
Pirim, Dilek [1 ]
Wang, Xingbin [1 ]
Radwan, Zaheda H. [1 ]
Niemsiri, Vipavee [1 ]
Hokanson, John E. [2 ]
Hamman, Richard F. [2 ]
Barmada, M. Michael [1 ]
Demirci, F. Yesim [1 ]
Kamboh, M. Ilyas [1 ]
机构
[1] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA
[2] Univ Colorado Denver, Dept Epidemiol, Colorado Sch Publ Hlth, Aurora, CO USA
基金
美国国家卫生研究院;
关键词
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;
D O I
10.1194/jlr.M043265
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:85 / 93
页数:9
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