Trial reportJournal of the American College of Cardiology2005
A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis.
Trial report in Journal of the American College of Cardiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 5 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 5 syntheses or guidelines pooled it, 159 citations in OpenAlex.
- Is a PCSK9 Inhibitor Right for Your Patient? A Review of Treatment Data for Individualized Therapy.International journal of environmental research and public health · 2022Pooled it
- LabWAS: Novel findings and study design recommendations from a meta-analysis of clinical labs in two independent biobanks.PLoS genetics · 2020Pooled 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
- The Influence of OLR1 and PCSK9 Gene Polymorphisms on Ischemic Stroke: Evidence from a Meta-Analysis.Scientific reports · 2015Pooled 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
- PCSK9 is a critical regulator of the innate immune response and septic shock outcome.Science translational medicine · 2014Trial
- Genetic variation at the PCSK9 locus moderately lowers low-density lipoprotein cholesterol levels, but does not significantly lower vascular disease risk in an elderly population.Atherosclerosis · 2008Trial
- First LDLRAP1 and Recurrent LDLR Mutations in Tunisian Families With Familial Hypercholesterolemia.Journal of cellular and molecular medicine · 2026Article
- Single nucleotide polymorphisms: Implications in the early diagnosis and targeted intervention of coronary microvascular dysfunction.Genes & diseases · 2025Review
- A commonly inherited human PCSK9 germline variant drives breast cancer metastasis via LRP1 receptor.Cell · 2025Article
- Exploring PCSK9 Genetic Impact on Lipoprotein(a) via Dual Approaches: Association and Mendelian Randomization.International journal of molecular sciences · 2023Article
- E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach?Frontiers in clinical diabetes and healthcare · 2023Article
- Low circulating PCSK9 levels inFrontiers in genetics · 2022Article
- Variations in TM6SF2, PCSK9 and PCSK7 genes and risk of hepatic steatosis after liver transplantation: a cross-sectional study.BMC gastroenterology · 2021Article
- Antibody-Based Therapeutics for Atherosclerosis and Cardiovascular Diseases.International journal of molecular sciences · 2021Review
- Effect ofThe International journal of angiology : official publication of the International College of Angiology, Inc · 2021Review
- Patterns and tempo of PCSK9 pseudogenizations suggest an ancient divergence in mammalian cholesterol homeostasis mechanisms.Genetica · 2021Article
- Variations of the proprotein convertase subtilisin/kexin type 9 gene in coronary artery disease.The Journal of international medical research · 2020Article
- Review
- 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
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesWe sought to determine the effects of PCSK9 variants on plasma low-density lipoprotein cholesterol (LDL-C) levels, severity of coronary atherosclerosis, and response to statin therapy in the Lipoprotein Coronary Atherosclerosis Study (LCAS) population.
backgroundMutations in PCSK9 cause autosomal-dominant hypercholesterolemia. We hypothesized that PCSK9 variants could affect plasma LDL-C in individuals with polygenic hypercholesterolemia.
methodsWe sequenced all 12 exons and boundaries to detect novel polymorphisms, and genotyped 372 subjects in LCAS and 319 subjects in a second independent population for six polymorphisms, including novel leucine repeats, by fluorescently tagged markers. We reconstructed haplotypes using a Bayesian algorithm.
resultsPermutation test results showed statistically significant differences in global haplotype distribution among the tertiles of LDL-C (odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.90 to 4.32, p = 0.005) and minimum lumen diameter of coronary lesions (OR: 1.83, 95% CI: 1.01 to 3.55, p = 0.045). Regression analysis identified haplotype 3 as an independent determinant of LDL-C levels (adjusted R2 = 2.2%, F = 9.37, p = 0.002). Haplotype structure analysis identified E670G as the determinant variant, exerting a dose effect (GG > EG > EE) and accounting for 3.5% of plasma LDL-C variability (F = 14.6, p < 0.001). Plasma total cholesterol, apolipoprotein B, and lipoprotein (a) levels were also associated with the E670G variant. Distributions of the E670G genotypes in an independent normolipidemic and the hyperlipidemic LCAS populations were significantly different (F = 7.2, p = 0.027). No significant treatment-by-genotype interactions were detected. The false positive report probability was between 2% and 8%.
conclusionsHaplotype 3 encompassing the E670G variant is an independent determinant of plasma LDL-C levels and the severity of coronary atherosclerosis.
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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.