ArticleCirculation. Cardiovascular genetics2009
Genetic variation at the proprotein convertase subtilisin/kexin type 5 gene modulates high-density lipoprotein cholesterol levels.
Article in Circulation. Cardiovascular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 4 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Cord blood epigenome-wide meta-analysis in six European-based child cohorts identifies signatures linked to rapid weight growth.BMC medicine · 2023Pooled it
- Genetic and clinical determinants of abdominal aortic diameter: genome-wide association studies, exome array data and Mendelian randomization study.Human molecular genetics · 2022Pooled it
- Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.American journal of epidemiology · 2019Pooled it
- Dense genotyping of candidate gene loci identifies variants associated with high-density lipoprotein cholesterol.Circulation. Cardiovascular genetics · 2011Pooled it
- PCSK5 promotes angiogenesis and cardiac repair after myocardial infarction.Nature communications · 2026Article
- Whole genome sequencing of mouse lines divergently selected for fatness (FLI) and leanness (FHI) revealed several genetic variants as candidates for novel obesity genes.Genes & genomics · 2024Article
- Genome-wide screening for genetic variants in polyadenylation signal (PAS) sites in mouse selection lines for fatness and leanness.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Article
- Therapeutic potential of the Proprotein Convertase Subtilisin/Kexin family in vascular disease.Frontiers in pharmacology · 2022Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Molecular evolution of PCSK family: Analysis of natural selection rate and gene loss.PloS one · 2021Article
- Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis.Molecular systems biology · 2021Article
- Genome-wide association studies for 30 haematological and blood clinical-biochemical traits in Large White pigs reveal genomic regions affecting intermediate phenotypes.Scientific reports · 2019Article
- Genetics of pleiotropic effects of dexamethasone.Pharmacogenetics and genomics · 2017Article
- Genetic determinants of inherited susceptibility to hypercholesterolemia - a comprehensive literature review.Lipids in health and disease · 2017Review
- Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model.BMC medical genomics · 2014Article
- Genetics of the first seven proprotein convertase enzymes in health and disease.Current genomics · 2013Article
- Proprotein convertases play an important role in regulating PKGI endoproteolytic cleavage and nuclear transport.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Laser-capture microdissection and transcriptional profiling of the dorsomedial nucleus of the hypothalamus.The Journal of comparative neurology · 2012Article
- Biallelic expression of Tbx1 protects the embryo from developmental defects caused by increased receptor tyrosine kinase signaling.Developmental dynamics : an official publication of the American Association of Anatomists · 2012Article
- Genetics of cholesterol efflux.Current atherosclerosis reports · 2012Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundA 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
resultsHaplotypes 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 SNPs (n=182 total) in 457 individuals with documented coronary artery disease. We identified 9 SNPs associated with HDL-C (P<0.05), with the strongest results for rs11144782 and rs11144766 (P=0.002 and P=0.005, respectively). The SNP rs11144782 was also associated with very low-density lipoprotein (P=0.039), triglycerides (P=0.049), and total apolipoprotein levels (P=0.022). In stage 2, we replicated the association of rs11144766 with HDL-C (P=0.014) in an independent sample of Finnish low HDL-C families. In a combined analysis of both stages (n=883), region-wide significance of rs11144766 and low HDL-C was observed (unadjusted P=1.86x10(-4) and Bonferroni-adjusted P=0.031).
conclusionsWe conclude that variability at the PCSK5 locus influences HDL-C levels, possibly through the inactivation of endothelial lipase activity, and, consequently, atherosclerotic cardiovascular disease risk.
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