There are approximately 12 million statin users in the United Kingdom. Approximately 9% of users present with intolerance to statins, manifesting as muscle ache, fatigue or more seriously, muscle breakdown leading to myopathy. Creatine phosphokinase (CK) levels are used as a biomarker of statin-induced muscle damage. Variants in LILRB5 and CKM were shown to be associated with CK levels irrespective of statin usage. This study aims to analyse the association of these variants with statin intolerance.Genotype information was gathered for two missense variants, rs12975366 (LILRB5: Asp247Gly) and rs11559024 (CKM: Glu83Gly) in the GoDARTS study cohort of Scottish Caucasian individuals in the Tayside and Fife areas. We found both variants were associated with CK levels in statin users and non-users, but that only Asp247Gly was associated with our definition of statin intolerance (raised CK and accompanying prescribing changes) : OR 0.48, p value 7.7 x 10 ⁻⁵ and 95% CI (0.28, 0.65).This demonstrates that the LILRB5 locus is associated with statin intolerance-related raised CK levels, whereas CKM is purely a marker of constitutional serum CK levels. This study also highlights the probability that statin intolerant individuals may not have raised CK levels for genetic reasons.This study presents a novel genetic factor associated with statin intolerance and raises considerations for the usage of CK as a biomarker. It encourages further investigation into the physiology of statin-induced muscle damage, inter-individual variability in CK levels and response to muscle damage.
|Publication status||Published - 6 Oct 2015|
|Event||65th American Society of Human Genetics Annual Meeting - Baltimore Convention Center, Baltimore, United States|
Duration: 6 Oct 2015 → 10 Oct 2015
http://www.ashg.org/2015meeting/ (Link to Conference website)
|Conference||65th American Society of Human Genetics Annual Meeting|
|Abbreviated title||ASHG 2015|
|Period||6/10/15 → 10/10/15|
Siddiqui, M. K., Veluchamy, A., Tavendale, R., Carr, F., Maroteau, C., Pearson, E. R., Looker, H. M., Morris, A. D., Dow, E., George, J., Doney, A., & Palmer, C. N. A. (2015). A common missense variant of LILRB5 is associated with statin intolerance: A GoDARTS study. Poster session presented at 65th American Society of Human Genetics Annual Meeting, Baltimore, United States.