Pharmacogenetics of statin-induced muscle toxicity: exploration using the UK General Practice Research Database (G

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Statins are associated with myotoxicity, but to date, studies investigating genetic predisposition have been small and inconclusive. In the application, we propose the first ever use of GPRD to conduct a pharmacogenetic study. We propose a case-control study design, with patients recruited via GPRD practices. Cases will be patients with a creatine phosphokinase (CPK) level of at least 2x upper limit of normal during statin exposure in presence or absence of muscle symptoms. Saliva sample and patient questionnaires will be collected from cases and controls. The patient questionnaire will include questions on risk factors for myopathy and also questions about the patients willingness to participate in this research. DNA will be analysed using a candidate gene approach, with relevant genes in pathways being assessed (pathway pharmacogentics). The candidate genes will be chosen on the basis of the known pharmacokinetic and pharmacodynamic characteristics of statins. The genes will be analysed for tag SNPs, functional variants and haplotypes, which will then be related to the change in CPK levels. The milestone for this study is to recruit 250 cases and 500 controls and analyse the data within 2 years of the start of the study.