Lipoprotein lipase gene sequencing and plasma lipid profile.
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.
['Pirim|Dilek|D|', 'Wang|Xingbin|X|', 'Radwan|Zaheda H|ZH|', 'Niemsiri|Vipavee|V|', 'Hokanson|John E|JE|', 'Hamman|Richard F|RF|', 'Barmada|M Michael|MM|', 'Demirci|F Yesim|FY|', 'Kamboh|M Ilyas|MI|']
D000328:Adult D000368:Aged D016022:Case-Control Studies D008076:Cholesterol, HDL D003924:Diabetes Mellitus, Type 2 D005260:Female D005787:Gene Frequency D056726:Genetic Association Studies D006239:Haplotypes D006801:Humans D015810:Linkage Disequilibrium D008071:Lipoprotein Lipase D008297:Male D008875:Middle Aged D058977:Molecular Sequence Annotation D020641:Polymorphism, Single Nucleotide D017422:Sequence Analysis, DNA D014280:Triglycerides
lipid metabolism triglycerides rare variants genotyping candidate gene genetic association