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A common missense variant of LILRB5 is associated with statin intolerance and myalgia
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
University of Dundee, Ninewells Hospital and Medical School, Pat McPherson Centre for Pharmacogenetics & Pharmacogenomics, Division of Molecular & Clinical Medicine.
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2017 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no 48, p. 3569-U31Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2017. Vol. 38, no 48, p. 3569-U31
Keyword [en]
Statins, Pharmacogenetics, Immunogenetics, Precision medicine, Adverse drug reactions, Myalgia
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-339765DOI: 10.1093/eurheartj/ehx467ISI: 000418697400011PubMedID: 29020356OAI: oai:DiVA.org:uu-339765DiVA: diva2:1179971
Funder
EU, FP7, Seventh Framework Programme, 602108Wellcome trust, 099177/Z/12/Z; 072960; 084726AstraZenecaSwedish Research Council, 521-2011-2440; 521-2014-3370Swedish Heart Lung Foundation, 20120557; 20140291
Available from: 2018-02-02 Created: 2018-02-02 Last updated: 2018-02-02Bibliographically approved

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