SLCO1B1 Genetic Variant Associated With Statin-Induced Myopathy: A Proof-of-Concept Study Using the Clinical Practice Research Datalink

D F Carr, H O'Meara, A L Jorgensen, J Campbell, M Hobbs, G McCann, T van Staa, M Pirmohamed
2013 Clinical Pharmacology and Therapeutics  
This study aimed to determine whether patients with statin-induced myopathy could be identified using the United Kingdom Clinical Practice Research Datalink, whether DNA could be obtained, and whether previously reported associations of statin myopathy with the SLCO1B1 c.521T>C and COQ2 rs4693075 polymorphisms could be replicated. Seventy-seven statin-induced myopathy patients (serum creatine phosphokinase (CPK) > 4× upper limit of normal (ULN)) and 372 statin-tolerant controls were identified
more » ... nd recruited. Multiple logistic regression analysis showed the SLCO1B1 c.521T>C single-nucleotide polymorphism to be a significant risk factor (P = 0.009), with an odds ratio (OR) per variant allele of 2.06 (1.32-3.15) for all myopathy and 4.09 (2.06-8.16) for severe myopathy (CPK > 10× ULN, and/ or rhabdomyolysis; n = 23). COQ2 rs4693075 was not associated with myopathy. Meta-analysis showed an association between c.521C>T and simvastatin-induced myopathy, although power for other statins was limited. Our data replicate the association of SLCO1B1 variants with statin-induced myopathy. Furthermore, we demonstrate how electronic medical records provide a time-and cost-efficient means of recruiting patients with severe adverse drug reactions for pharmacogenetic studies.
doi:10.1038/clpt.2013.161 pmid:23942138 pmcid:PMC3831180 fatcat:yl7gfqg5ijgsnb3k7225bztdkm