Evidence mapPaperPMID 29020356Full record

Trial reportEuropean heart journal2017

A common missense variant of LILRB5 is associated with statin intolerance and myalgia.

Moneeza K Siddiqui, Cyrielle Maroteau, Abirami Veluchamy, Aleksi Tornio, Roger Tavendale, Fiona Carr, Ngu-Uma Abelega, Dan Carr, Katyrzyna Bloch, Par Hallberg and 15 more

Open access · bronzeFull text readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in European heart journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 4 pooled it
5.0field-weighted citation impact, top 4% 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

22 citing papers in PubMed, 4 syntheses or guidelines pooled it, 53 citations in OpenAlex.

  1. Pooled it
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  15. Common Statin Intolerance Variants inFrontiers in genetics · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 9 institutions in 4 countries.

Moneeza K SiddiquiPat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
Cyrielle MaroteauPat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
Abirami VeluchamyPat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
Aleksi TornioPat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
Roger TavendalePat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
Fiona CarrPat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
Ngu-Uma AbelegaPat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
Dan CarrInstitute of Translation Medicine, University of Liverpool, Liverpool L69 3BX, UK.
Katyrzyna BlochInstitute of Translation Medicine, University of Liverpool, Liverpool L69 3BX, UK.
Par HallbergDepartment of Medical Sciences, Clinical Pharmacology and Science of Life Laboratory, Uppsala University, 751 85 Uppsala, Sweden.
Qun-Ying YueMedical Products Agency, Dag Hammarskjölds väg 42, 75237 Uppsala, Sweden.
Ewan R PearsonPat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
Helen M ColhounPat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
Andrew D MorrisPat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
Eleanor DowNinewells Hospital and Medical School, Dundee DD19SY, UK.
Jacob GeorgeNinewells Hospital and Medical School, Dundee DD19SY, UK.
Munir PirmohamedInstitute of Translation Medicine, University of Liverpool, Liverpool L69 3BX, UK.
Paul M RidkerBrigham and Women's Hospital, Department of Medicine, Preventive Medicine, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Alex S F DoneyNinewells Hospital and Medical School, Dundee DD19SY, UK.
Ana AlfirevicInstitute of Translation Medicine, University of Liverpool, Liverpool L69 3BX, UK.
Mia WadeliusDepartment of Medical Sciences, Clinical Pharmacology and Science of Life Laboratory, Uppsala University, 751 85 Uppsala, Sweden.
Anke-Hilse Maitland-van der ZeeDivision of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, 3508 TB Utrecht, The Netherlands.
Daniel I ChasmanBrigham and Women's Hospital, Department of Medicine, Preventive Medicine, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Colin N A PalmerPat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD19SY, UK.
PREDICTION-ADR Consortium
University of Dundee · GBNinewells Hospital · GBUniversity of Liverpool · GBUppsala University · SEBrigham and Women's Hospital · USHarvard University · USMedical Products Agency · SEUniversity of Edinburgh · GBUtrecht University · NL

Funding

Medical Research Council G0601261Medical Research Council MC_PC_13040Medical Research Council MC_QA137929Medical Research Council MR/K007017/1Medical Research Council MR/L006758/1Medical Research Council MR/M501633/1Medical Research Council MR/M501633/2Wellcome TrustWellcome Trust 072960Wellcome Trust 084726Wellcome Trust 099177/Z/12/Z
6 · The paper itself

Abstract

Aims: A genetic variant in LILRB5 (leukocyte immunoglobulin-like receptor subfamily-B) (rs12975366: T > C: Asp247Gly) has been reported to be associated with lower creatine phosphokinase (CK) and lactate dehydrogenase (LDH) levels. Both biomarkers are released from injured muscle tissue, making this variant a potential candidate for susceptibility to muscle-related symptoms. We examined the association of this variant with statin intolerance ascertained from electronic medical records in the GoDARTS study. Methods and results: In the GoDARTS cohort, the LILRB5 Asp247 variant was associated with statin intolerance (SI) phenotypes; one defined as having raised CK and being non-adherent to therapy [odds ratio (OR) 1.81; 95% confidence interval (CI): 1.34-2.45] and the other as being intolerant to the lowest approved dose of a statin before being switched to two or more other statins (OR 1.36; 95% CI: 1.07-1.73). Those homozygous for Asp247 had increased odds of developing both definitions of intolerance. Importantly the second definition did not rely on CK elevations. These results were replicated in adjudicated cases of statin-induced myopathy in the PREDICTION-ADR consortium (OR1.48; 95% CI: 1.05-2.10) and for the development of myalgia in the JUPITER randomized clinical trial of rosuvastatin (OR1.35, 95% CI: 1.10-1.68). A meta-analysis across the studies showed a consistent association between Asp247Gly and outcomes associated with SI (OR1.34; 95% CI: 1.16-1.54). Conclusion: This study presents a novel immunogenetic factor associated with statin intolerance, an important risk factor for cardiovascular outcomes. The results suggest that true statin-induced myalgia and non-specific myalgia are distinct, with a potential role for the immune system in their development. We identify a genetic group that is more likely to be intolerant to their statins.

Indexed as

Drug ToleranceMutation, MissenseAntigens, CDBiomarkersCreatine KinaseDNADNA Mutational AnalysisDyslipidemiasFemaleGenotypeHumansHydroxymethylglutaryl-CoA Reductase InhibitorsL-Lactate DehydrogenaseMaleMiddle AgedMyalgiaAntigens, CDBiomarkersCreatine KinaseDNAHydroxymethylglutaryl-CoA Reductase InhibitorsLILRB5 protein, humanL-Lactate DehydrogenaseReceptors, ImmunologicRosuvastatin CalciumAdverse drug reactionsImmunogeneticsMyalgiaPharmacogeneticsPrecision medicineStatins

Identifiers

PMID29020356
PMCPMC5837247
OpenAlexW2771232411

What Socratic holds

Textfull text, public
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.