Genetic factors and statin-induced muscle disease

Rachel Kinsey, Craig Webster, Alan Jones

Department of Biochemistry and Immunology, Birmingham Heartlands Hospital

Statins are commonly prescribed drugs that are used to lower cholesterol levels, thereby reducing the risk of heart and other circulatory diseases.  Statins rarely cause side-effects, however they can cause muscle problems (myopathy) such as pain, weakness and tenderness.  The mechanism for such side-effects is unknown, however there is evidence for an association between statin-induced myopathy and mutations in the gene SLCO1B1, which encodes the organic anion transporting polypeptide 1B1 (OATP1B1), a protein responsible for the uptake of statins into the liver.  Several single nucleotide polymorphisms (SNPs) within the SLCO1B1 gene, and methods for their detection, have been reported in the literature.  The aims of this study are to develop an in-house method for the detection of SLCO1B1 SNPs, and to test the apparent association between SLCO1B1 SNPs and statin-induced myopathy.  To date, conditions for a real-time PCR method for detection of SLCO1B1 SNPs have been optimised, and method validation is ongoing.  Once control samples have been identified for each SNP to be studied, they will be used in a real-time PCR assay to detect SLCO1B1 SNPs.  Approval from a Research Ethics Committee has been obtained to collect samples from patients that have had statin-induced myopathy; samples will also be collected from age, sex and ethnicity-matched control subjects who have not suffered side-effects due to statin therapy.  DNA will be extracted from the samples and analysed for SLCO1B1 SNPs, in order to test whether or not there is an association between SLCO1B1 SNPs and statin-induced myopathy.