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



Siddiqui, Moneeza K, Maroteau, Cyrielle, Veluchamy, Abirami, Tornio, Aleksi, Tavendale, Roger, Carr, Fiona, Abelega, Ngu-Uma, Carr, Dan ORCID: 0000-0001-8028-4282, Bloch, Katyrzyna, Hallberg, Par
et al (show 15 more authors) (2017) A common missense variant of LILRB5 is associated with statin intolerance and myalgia. EUROPEAN HEART JOURNAL, 38 (48). 3569 - 3U31.

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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.

Item Type: Article
Uncontrolled Keywords: Statins, Pharmacogenetics, Immunogenetics, Precision medicine, Adverse drug reactions, Myalgia
Depositing User: Symplectic Admin
Date Deposited: 10 Nov 2017 10:36
Last Modified: 29 Nov 2020 16:10
DOI: 10.1093/eurheartj/ehx467
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3010843