Projects per year
Abstract
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 (OR1.81;95%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.
Original language | English |
---|---|
Pages (from-to) | 3569-3575 |
Number of pages | 7 |
Journal | European Heart Journal |
Volume | 38 |
Issue number | 48 |
Early online date | 29 Aug 2017 |
DOIs | |
Publication status | Published - 21 Dec 2017 |
Keywords
- Statins
- Pharmacogenetics
- Immunogenetics
- Precision medicine
- Adverse Drug Reactions
- Myalgia
Fingerprint
Dive into the research topics of 'A common missense variant of LILRB5 is associated with statin intolerance and myalgia'. Together they form a unique fingerprint.Projects
- 2 Finished
-
PREDICTION-ADR: Personalisation of tREatment In Cardiovascular Disease Through Next Generation Sequencing - Adverse Drug Reactions (Joint with University of Uppsala, University of Liverpool and University of Utrecht)
Palmer, C. (Investigator)
COMMISSION OF THE EUROPEAN COMMUNITIES
1/09/13 → 28/02/17
Project: Research
-
The Scottish eHealth Informatics Research Centre (E-HIRCs) (Joint with Universities of Aberdeen, Glasgow, Edinburgh, Strathclyde, St Andrews & Leicester and ISD)
Colhoun, H. (Investigator), Donnan, P. (Investigator), Guthrie, B. (Investigator), Jefferson, E. (Investigator), MacDonald, T. (Investigator), McCowan, C. (Investigator), Morris, A. (Investigator), Pearson, E. (Investigator), Sullivan, F. (Investigator) & Swedlow, J. (Investigator)
1/03/13 → 31/12/18
Project: Research
Profiles
-
Palmer, Colin
- Population Health and Genomics - Professor (Teaching and Research) of Pharmacogenomics
Person: Academic