Genetic Variation at the Proprotein Convertase Subtilisin/Kexin Type 5 Gene Modulates High-Density Lipoprotein Cholesterol Levels
- 1 October 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation: Cardiovascular Genetics
- Vol. 2 (5), 467-475
- https://doi.org/10.1161/circgenetics.109.877811
Abstract
Background— A low level of plasma high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. HDL particles are modulated by a variety of lipases, including endothelial lipase, a phospholipase present on vascular endothelial cells. The proprotein convertase subtilisin/kexin type 5 (PCSK5) gene product is known to directly inactivate endothelial lipase and indirectly cleave and activate angiopoetin-like protein 3, a natural inhibitor of endothelial lipase. We therefore investigated the effect of human PCSK5 genetic variants on plasma HDL-C levels. Methods and Results— Haplotypes at the PCSK5 locus were examined in 9 multigenerational families that included 60 individuals with HDL-C <10th percentile. Segregation with low HDL-C in 1 family was found. Sequencing of the PCSK5 gene in 12 probands with HDL-C <5th percentile identified 7 novel variants. Using a 2-stage design, we first genotyped these single-nucleotide polymorphisms (SNPs) along with 163 tagSNPs and 12 additional SNP...Keywords
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