ArticleThe Journal of clinical endocrinology and metabolism2015
Both rare and common variants in PCSK9 influence plasma low-density lipoprotein cholesterol level in American Indians.
Article in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 3 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 3 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Pooled it
- Pooled it
- The associations between proprotein convertase subtilisin/kexin type 9 E670G polymorphism and the risk of coronary artery disease and serum lipid levels: a meta-analysis.Lipids in health and disease · 2015Pooled it
- Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026Article
- Correlation of Eight (8) Polymorphisms and Their Genotypes with the Risk Factors of Cardiovascular Disease in a Black Elderly Population.Current issues in molecular biology · 2024Article
- Association of Low-Density Lipoprotein Cholesterol Levels with More than 20-Year Risk of Cardiovascular and All-Cause Mortality in the General Population.Journal of the American Heart Association · 2022Article
- Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver transplantation: a cross-sectional study.BMC gastroenterology · 2021Article
- Genetic variation and urine cadmium levels: ABCC1 effects in the Strong Heart Family Study.Environmental pollution (Barking, Essex : 1987) · 2021Article
- Characterization of LDLR rs5925 and PCSK9 rs505151 genetic variants frequencies in healthy subjects from northern Chile: Influence on plasma lipid levels.Journal of clinical laboratory analysis · 2019Article
- A novel study to examine the association ofJournal of genetics · 2018Article
- Phenotype-Specific Enrichment of Mendelian Disorder Genes near GWAS Regions across 62 Complex Traits.American journal of human genetics · 2018Article
- Serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk and lipid profiles in southern Chinese Han population.Lipids in health and disease · 2018Article
- Malaria severity: Possible influence of the E670G PCSK9 polymorphism: A preliminary case-control study in Malian children.PloS one · 2018Article
- PCSK9 Mutations in Familial Hypercholesterolemia: from a Groundbreaking Discovery to Anti-PCSK9 Therapies.Current atherosclerosis reports · 2017Review
- Association of the variants and haplotypes in the DOCK7, PCSK9 and GALNT2 genes and the risk of hyperlipidaemia.Journal of cellular and molecular medicine · 2016Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
contextElevated LDL cholesterol (LDL-C) is an important risk factor for atherosclerosis and cardiovascular disease. Variants in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene have been associated not only with plasma LDL-C concentration, but also with ischemic heart disease. Little is known about the genetic architecture of PCSK9 and its influence on LDL-C in American Indians.
objectiveWe aimed to investigate the genetic architecture in the 1p32 region encompassing PCSK9 and its influence on LDL-C in American Indians.
designThe Strong Heart Family Study (SHFS) is a family-based genetic study.
participantsTwo thousand four hundred fifty eight American Indians from Arizona, Oklahoma, North Dakota, and South Dakota, who were genotyped by Illumina MetaboChip.
resultsWe genotyped 486 SNPs in a 3.9 Mb region at chromosome 1p32 encompassing PCSK9 in 2458 American Indians. We examined the association between these SNPs and LDL-C. For common variants (MAF ≥ 1%), meta-analysis across the three geographic regions showed common variants in PCSK9 were significantly associated with higher LDL-C. The most significant SNP rs12067569 (MAF = 1.7 %, β = 16.9 ± 3.7, P = 5.9 × 10(-6)) was in complete LD (r(2) = 1) with a nearby missense SNP, rs505151 (E670G) (β = 15.0 ± 3.6, P = 3.6 × 10(-5)). For rare variants (MAF < 1%), rs11591147 (R46L, MAF = 0.9%) was associated with lower LDL-C (β = - 31.1 ± 7.1, P = 1.4 × 10(-5)). The mean (SD) of LDL-C was 76.9 (7.8) and 107.4 (1.0) mg/dL for those with and without the R46L mutation, respectively. One person who was homozygous for R46L had LDL-C levels of 11 mg/dL. In one family, 6 out of 8 members carrying the R46L mutation had LDL-C levels below the lower 10% percentile of LDL-C among all study participants.
conclusionsBoth rare and common variants in PCSK9 influence plasma LDL-C levels in American Indians. Follow-up studies may disclose the influence of these mutations on the risk of CVD and responses to cholesterol-lowering medications.
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