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dc.contributor.authorK Siddiqui, Moneezaen_US
dc.contributor.authorMaroteau, Cyrielleen_US
dc.contributor.authorVeluchamy, Abiramien_US
dc.contributor.authorTornio, Aleksien_US
dc.contributor.authorTavendale, Rogeren_US
dc.contributor.authorCarr, Fionaen_US
dc.contributor.authorAbelega, Ngu-Umaen_US
dc.contributor.authorCarr, Danen_US
dc.contributor.authorBloch, Katyrzynaen_US
dc.contributor.authorHallberg, Paren_US
dc.contributor.authorYue, Qun-Yingen_US
dc.contributor.authorPearson, Ewan Ren_US
dc.contributor.authorColhoun, Helen Men_US
dc.contributor.authorMorris, Andrew Den_US
dc.contributor.authorDow, Eleanoren_US
dc.contributor.authorGeorge, Jacoben_US
dc.contributor.authorPirmohamed, Muniren_US
dc.contributor.authorRidker, Paul Men_US
dc.contributor.authorDoney, Alex S Fen_US
dc.contributor.authorAlfirevic, Anaen_US
dc.contributor.authorWadelius, Miaen_US
dc.contributor.authorMaitland-van der Zee, Anke-Hilseen_US
dc.contributor.authorChasman, Daniel Ien_US
dc.contributor.authorPalmer, Colin N Aen_US
dc.date.accessioned2018-04-19T14:22:57Z
dc.date.issued2017en_US
dc.identifier.citationK Siddiqui, M., C. Maroteau, A. Veluchamy, A. Tornio, R. Tavendale, F. Carr, N. Abelega, et al. 2017. “A common missense variant of LILRB5 is associated with statin intolerance and myalgia.” European Heart Journal 38 (48): 3569-3575. doi:10.1093/eurheartj/ehx467. http://dx.doi.org/10.1093/eurheartj/ehx467.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:35982161
dc.description.abstractAbstract 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.en
dc.language.isoen_USen
dc.publisherOxford University Pressen
dc.relation.isversionofdoi:10.1093/eurheartj/ehx467en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837247/pdf/en
dash.licenseLAAen_US
dc.subjectPrevention and Epidemiologyen
dc.subjectStatinsen
dc.subjectPharmacogeneticsen
dc.subjectImmunogeneticsen
dc.subjectPrecision medicineen
dc.subjectAdverse drug reactionsen
dc.subjectMyalgiaen
dc.titleA common missense variant of LILRB5 is associated with statin intolerance and myalgiaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalEuropean Heart Journalen
dash.depositing.authorRidker, Paul Men_US
dc.date.available2018-04-19T14:22:57Z
dc.identifier.doi10.1093/eurheartj/ehx467*
dash.authorsorderedfalse
dash.contributor.affiliatedRidker, Paul
dash.contributor.affiliatedChasman, Daniel


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