ArticleThe New England journal of medicine2014
Loss-of-function mutations in APOC3, triglycerides, and coronary disease.
Article in The New England journal of medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 522 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
522 citing papers in PubMed, 5 syntheses or guidelines pooled it, 1,055 citations in OpenAlex.
- The Efficacy and Safety of Plozasiran on Lipid Profile in Dyslipidemic Disorders: A Systematic Review and Meta-Analysis.Cardiovascular drugs and therapy · 2026Pooled it
- Olezarsen in Hypertriglyceridemia With High Cardiac Risk: A GRADE-Assessed Meta-Analysis of Randomized Trials With Trial Sequential Evidence.Endocrinology, diabetes & metabolism · 2026Pooled it
- Genetic Assessment and Clinical Correlates in Severe Hypertriglyceridemia: A Systematic Review.Genes · 2025Pooled it
- Volanesorsen to treat severe hypertriglyceridaemia: A pooled analysis of randomized controlled trials.European journal of clinical investigation · 2022Pooled it
- Inframe insertion and splice site variants in MFGE8 associate with protection against coronary atherosclerosis.Communications biology · 2022Pooled it
- Safety, pharmacokinetics and pharmacodynamics of Plozasiran in Chinese healthy volunteers.Cardiovascular diabetology · 2025Trial
- Postprandial metabolism of apolipoproteins B48, B100, C-III, and E in humans with APOC3 loss-of-function mutations.JCI insight · 2022Trial
- Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk.European heart journal · 2022Trial
- Rare, Damaging DNA Variants inCirculation. Genomic and precision medicine · 2021Trial
- Review
- Targeting triglycerides for cardiovascular risk reduction.Internal and emergency medicine · 2026Review
- Article
- Triglyceride-Rich Lipoproteins and ASCVD: Evidence for Causality and Challenges in Therapeutic Translation.Current atherosclerosis reports · 2026Review
- Spatial Glyco-Codes Define Human Liver Pathology and Progression.bioRxiv : the preprint server for biology · 2026Article
- Review
- Biologics for cardiovascular diseases: from bench to bedside.Signal transduction and targeted therapy · 2026Review
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Triglyceride-Rich Lipoprotein Metabolism and Cardiovascular Risk in Diabetes: Bedside to Bench to Bedside.Circulation research · 2026Review
- Kidney-Vascular Metabolic Crosstalk: Altered Lipoproteins in CKD.Circulation research · 2026Review
- Use of plozasiran across a spectrum of hypertriglyceridemia: Long-term efficacy and safety data from the open-label extension period of SHASTA-2 and MUIR Trials.American journal of preventive cardiology · 2026Article
462 more citing papers are in PubMed but not listed here.
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Authors and funding
87 authors.
Funding
Abstract
backgroundPlasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype.
methodsWe sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons.
resultsAn aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P=8×10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P=4×10(-6)).
conclusionsRare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.).
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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.