Evidence map›Paper›PMID 27114411›Full record

ArticleCirculation. Cardiovascular genetics2016

Metabolic Characterization of a Rare Genetic Variation Within APOC3 and Its Lipoprotein Lipase-Independent Effects.

Fotios Drenos, George Davey Smith, Mika Ala-Korpela, Johannes Kettunen, Peter Würtz, Pasi Soininen, Antti J Kangas, Caroline Dale, Debbie A Lawlor, Tom R Gaunt and 2 more

Open access · diamondAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Cardiovascular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.

  1. Pooled it
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  10. Towards quality assurance and quality control in untargeted metabolomics studies.Metabolomics : Official journal of the Metabolomic Society · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Fotios DrenosFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.). n.j.timpson@bris.ac.uk f.drenos@bristol.ac.uk.
George Davey SmithFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.).
Mika Ala-KorpelaFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.).
Johannes KettunenFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.).
Peter WürtzFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.).
Pasi SoininenFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.).
Antti J KangasFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.).
Caroline DaleFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.).
Debbie A LawlorFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.).
Tom R GauntFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.).
Juan-Pablo CasasFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.).
Nicholas J TimpsonFrom the MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol (F.D., G.D.S., M.A.-K., D.A.L., T.R.G., N.J.T.); Institute of Cardiovascular Science, University College London, London, United Kingdom (F.D., C.D., J.-P.C.); Computational Medicine, Faculty of Medicine, University of Oulu & Biocenter Oulu, Oulu (M.A.-K., J.K., P.W., P.S., A.J.K.); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio (M.A.-K., J.K., P.S.); Public Health Genomics Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland (J.K.); and Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom (C.D., J.-P.C.). n.j.timpson@bris.ac.uk f.drenos@bristol.ac.uk.
University of Eastern Finland · FIUniversity of Oulu · FIUniversity College London · GBFinnish Institute for Health and Welfare · FI

Funding

British Heart Foundation PG/13/66/30442British Heart Foundation SP/07/008/24066Medical Research Council MC_PC_15018Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/3Medical Research Council MC_UU_12013/5Wellcome Trust 102215Wellcome Trust 202802/Z/16/Z
6 · The paper itself

Abstract

backgroundPlasma triglyceride levels have been implicated in atherosclerosis and coronary heart disease. Apolipoprotein C-III (APOC3) plays a key role in the hydrolysis of triglyceride-rich lipoproteins to remnant particles by lipoprotein lipase (LPL) and their uptake by the liver. A rare variant in APOC3(rs138326449) has been associated with triglyceride, very low-density lipoprotein, and high-density lipoprotein levels, as well as risk of coronary heart disease. We aimed to characterize the impact of this locus across a broad set of mainly lipids-focused metabolic measures. METHODS AND

resultsA high-throughput serum nuclear magnetic resonance metabolomics platform was used to quantify 225 metabolic measures in 13 285 participants from 2 European population cohorts. We analyzed the effect of the APOC3 variant on the metabolic measures and used the common LPL(rs12678919) polymorphism to test for LPL-independent effects. Eighty-one metabolic measures showed evidence of association with APOC3(rs138326449). In addition to previously reported triglyceride and high-density lipoprotein associations, the variant was also associated with very low-density lipoprotein and high-density lipoprotein composition measures, other cholesterol measures, and fatty acids. Comparison of the APOC3 and LPL associations revealed that APOC3 association results for medium and very large very low-density lipoprotein composition are unlikely to be solely predictable by the action of APOC3 through LPL.

conclusionsWe characterized the effects of the rare APOC3(rs138326449) loss of function mutation in lipoprotein metabolism, as well as the effects of LPL(rs12678919). Our results improve our understanding of the role of APOC3 in triglyceride metabolism, its LPL independent action, and the complex and correlated nature of human metabolites.

Indexed as

Polymorphism, Single NucleotideAdolescentAdultAgedApolipoprotein C-IIIAtherosclerosisBiomarkersChildDyslipidemiasFemaleGene FrequencyGenotypeHigh-Throughput Screening AssaysHumansHypolipidemic AgentsLipoprotein LipaseApolipoprotein C-IIIBiomarkersHypolipidemic AgentsISIS 304801Lipoprotein LipaseLipoproteins, HDLLipoproteins, VLDLLPL protein, humanOligonucleotidesTriglyceridesassociation studiesgeneticslipidsLPLmetabolismtriglyceridesVLDL

Identifiers

PMID27114411
PMCPMC4920206
OpenAlexW2342541891

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Registered trials

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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.