Evidence map›Paper›PMID 32494907›Full record

ArticleMetabolomics : Official journal of the Metabolomic Society2020

Metabolic characterisation of disturbances in the APOC3/triglyceride-rich lipoprotein pathway through sample-based recall by genotype.

Laura J Corbin, David A Hughes, Andrew J Chetwynd, Amy E Taylor, Andrew D Southam, Andris Jankevics, Ralf J M Weber, Alix Groom, Warwick B Dunn, Nicholas J Timpson

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Metabolomics : Official journal of the Metabolomic Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 34% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Laura J CorbinMRC Integrative Epidemiology Unit at University of Bristol, Bristol, BS8 2BN, UK.ORCID http://orcid.org/0000-0002-4032-9500
David A HughesMRC Integrative Epidemiology Unit at University of Bristol, Bristol, BS8 2BN, UK.
Andrew J ChetwyndSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Amy E TaylorPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, UK.
Andrew D SouthamSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Andris JankevicsSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Ralf J M WeberSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Alix GroomMRC Integrative Epidemiology Unit at University of Bristol, Bristol, BS8 2BN, UK.
Warwick B DunnSchool of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Nicholas J TimpsonMRC Integrative Epidemiology Unit at University of Bristol, Bristol, BS8 2BN, UK. n.j.timpson@bristol.ac.uk.
University of Birmingham · GBUniversity of Bristol · GBUniversity Hospitals Bristol NHS Foundation Trust · GB

Funding

Cancer Research UK C18281/A19169Medical Research Council MC_PC_15018Medical Research Council MC_PC_19009Medical Research Council MC_UU_00011Medical Research Council MC_UU_12013/3Medical Research Council MR/M009157/1Wellcome TrustWellcome Trust 102215/2/13/2Wellcome Trust 202802/Z/16/Z
6 · The paper itself

Abstract

introductionHigh plasma triacylglyceride levels are known to be associated with increased risk of atherosclerotic cardiovascular disease. Apolipoprotein C-III (apoC-III) is a key regulator of plasma triacylglyceride levels and is associated with hypertriglyceridemia via a number of pathways. There is consistent evidence for an association of cardiovascular events with blood apoC-III level, with support from human genetic studies of APOC3 variants. As such, apoC-III has been recognised as a potential therapeutic target for patients with severe hypertriglyceridaemia with one of the most promising apoC-III-targeting drugs, volanesorsen, having recently progressed through Phase III trials.

objectivesTo exploit a rare loss of function variant in APOC3 (rs138326449) to characterise the potential long-term treatment effects of apoC-III targeting interventions on the metabolome.

methodsIn a recall-by-genotype study, 115 plasma samples were analysed by UHPLC-MS to acquire non-targeted metabolomics data. The study included samples from 57 adolescents and 33 adults. Overall, 12 985 metabolic features were tested for an association with APOC3 genotype.

results161 uniquely annotated metabolites were found to be associated with rs138326449(APOC3). The highest proportion of associated metabolites belonged to the acyl-acyl glycerophospholipid and triacylglyceride metabolite classes. In addition to the anticipated (on-target) reduction of metabolites in the triacylglyceride and related classes, carriers of the rare variant exhibited previously unreported increases in levels of a number of metabolites from the acyl-alkyl glycerophospholipid class.

conclusionOverall, our results suggest that therapies targeting apoC-III may potentially achieve a broad shift in lipid profile that favours better metabolic health.

Indexed as

AdolescentAdultApolipoprotein C-IIIFemaleGenotypeHumansHypertriglyceridemiaLipidsLipoproteinsMaleMetabolomeMetabolomicsTriglyceridesYoung AdultAPOC3 protein, humanApolipoprotein C-IIILipidsLipoproteinslipoprotein triglycerideTriglyceridesALSPACAPOC3GenotypeMetabolitesRecall-by-genotypeTriglyceride-rich lipoprotein

Identifiers

PMID32494907
PMCPMC7270992
OpenAlexW3029963856

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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.