OATP-C(OATP01B1)*15 is associated with statin-induced myopathy in hypercholesterolemic patients

Abstract

Background Statins are associated with muscle complaints ranging from myalgia to rhabdomyolysis. We studied the genetic contribution to the risk of the statin-induced myopathy by comparing frequencies of mutant alleles of candidate genes in case and control groups. Methods We studied ten Japanese patients with abnormal increase in plasma creatinine kinase or severe muscle complaints, in comparison with control patients (n=26) who received statins but had no myopathy. DNA samples were genotyped for 152 SNPs/mutations in eight candidate genes selected from genes responsible for inherited rhabdomyolysis and those involved in the metabolism or transport of stains. Results No mutations or SNPs were detected in the genes of inherited rhabdomyolysis except for 128G>A in VLCAD, of which frequency was almost the same as that of the controls. For CYP3A4 and MRP2, one and two SNPs were detected respectively, but there was no significant difference between the groups. However, we found a significant association between OATP-C*15 and pravastatin- or atorvastatin-induced myopathy (P<0.01). An odds ratio of 11.3 (95%CI=1.6–80.3, P<0.05) was obtained when the possession of one or more OATP-C*15 was compared. In addition, an association between 2677G>A in MDR1 and simvastatin- or atorvastatin-incuced myopathy was also observed (P<0.05). Conclusions The results suggest that OATP-C*15 is one of the susceptible factors for development of myopathy in patients taking pravastatin or atorvastatin. Clinical Pharmacology & Therapeutics (2005) 77, P21–P21; doi: 10.1016/j.clpt.2004.11.081