ArticlePharmacogenetics and genomics2008
Molecular population genetics of PCSK9: a signature of recent positive selection.
Article in Pharmacogenetics and genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 5 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 5 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Pooled it
- Meta-GWAS of PCSK9 levels detects two novel loci at APOB and TM6SF2.Human molecular genetics · 2022Pooled it
- The association of the PCSK9 rs562556 polymorphism with serum lipids level: a meta-analysis.Lipids in health and disease · 2019Pooled it
- Differential effects of PCSK9 variants on risk of coronary disease and ischaemic stroke.European heart journal · 2018Pooled it
- What is the impact of PCSK9 rs505151 and rs11591147 polymorphisms on serum lipids level and cardiovascular risk: a meta-analysis.Lipids in health and disease · 2017Pooled it
- Association of positively selected eIF3a polymorphisms with toxicity of platinum-based chemotherapy in NSCLC patients.Acta pharmacologica Sinica · 2015Trial
- PCSK9 and Lipid Metabolism: Genetic Variants, Current Therapies, and Cardiovascular Outcomes.Cardiovascular drugs and therapy · 2025Review
- Genetic Risk Profiles for Atherosclerosis and Venous Thromboembolism in Azorean and Mainland Portuguese Populations: A Comparative Analysis.Current issues in molecular biology · 2025Article
- Can AI reveal the next generation of high-impact bone genomics targets?Bone reports · 2025Review
- A commonly inherited human PCSK9 germline variant drives breast cancer metastasis via LRP1 receptor.Cell · 2025Article
- Common and RareInternational journal of molecular sciences · 2022Article
- Screening of PCSK9 and LDLR genetic variants in Familial Hypercholesterolemia (FH) patients in India.Journal of human genetics · 2021Article
- Review
- Association of the rs562556 PCSK9 Gene Polymorphism with Reduced Mortality in Severe Malaria among Malian Children.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2020Article
- Malaria severity: Possible influence of the E670G PCSK9 polymorphism: A preliminary case-control study in Malian children.PloS one · 2018Article
- A Review of Pathway-Based Analysis Tools That Visualize Genetic Variants.Frontiers in genetics · 2017Review
- My Approach to the Patient With Familial Hypercholesterolemia.Mayo Clinic proceedings · 2016Review
- Both rare and common variants in PCSK9 influence plasma low-density lipoprotein cholesterol level in American Indians.The Journal of clinical endocrinology and metabolism · 2015Article
- Proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism interacts with alcohol consumption to modulate serum lipid levels.International journal of medical sciences · 2013Article
- The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations.Lipids in health and disease · 2011Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
objectiveProprotein convertase subtilisin-like kexin type 9 (PCSK9) is a newly discovered serine protease that plays a key role in regulating plasma low density lipoprotein (LDL) cholesterol levels. Both rare mutations and common variants in the coding regions of PCSK9 affect LDL cholesterol levels and coronary heart disease risk, as well as response to lipid-lowering therapy.
methodsThe authors characterized the patterns of variation at the PCSK9 locus in African-Americans and European-Americans using resequenced data from the SeattleSNPs database (pga.gs.washington.edu). The authors performed a test of population differentiation and the long-range haplotype test to detect signatures of recent position selection on PCSK9.
resultsA significantly high FST (a measure of population differentiation) between African-Americans and European-Americans was noted for single nucleotide polymorphism (SNP) rs505151 (FST=0.309). The long-range haplotype test was suggestive of non-neutral evolution of two SNPs, rs505151 and rs562556 that are associated with elevated LDL cholesterol levels ('gain-of-function' mutations). The modes of selection were different between African-Americans and European-Americans. The authors observed signals of recent positive selection on the ancestral allele of nonsynonymous SNP rs505151 (E670G, P=0.0227 and P=0.0001 in theoretical and empirical distribution, respectively) and the derived allele of nonsynonymous SNP rs562556 (I474V, P=0.0227 and 0.0001) in African-Americans, whereas in European-Americans the ancestral allele of SNP rs562556 (P=0.1320 and 0.0370) appeared to be under positive selection.
conclusionThe authors' findings suggest that evolutionary dynamics may underlie the 'gain-of-function' mutations in PCSK9 that are associated with higher LDL cholesterol levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.