Interindividual differences in the response to statin therapy and gene polymorphisms related to myopathy during statin therapy

Abstract

The enzyme HMG-CoA reductase (HMGCR), the main site of action of statins, undergoes alternative splicing of exon 13, which encodes the binding domain of statins to the enzyme. The resulting isoform, called HMGCRv1, shows altered enzyme activity and sensitivity to statins compared to the classical isoform. This translates into interindividual differences in the response to treatment with these drugs. A recent discovery in the field of genetics has brought about the identification of the single nucleotide polymorphism rs4363657 of the SLCO1B1 gene located on chromosome 12. This polymorphism is strongly associated with myopathy induced by statins. From the available literature, a clinical study has evaluated the relationship between gene polymorphisms and myopathy during statin therapy. The study involved 12 000 patients treated with simvastatin at a dose of 80 mg/day. The odds ratio for myopathy was 4.5 (95% confidence interval 2.6-7.7) per copy of the C allele, and 16.9 (95% confidence interval 4.7-61.1) in CC as compared with TT homozygotes. Myopathy could be attributed to the C variant in more than 60% of cases. Genomic typing may allow the identification of these variants, leading to a tailored statin therapy with higher benefits to the patients and less adverse side effects.