SLCO1B1 variants and statin-induced myopathy--a genomewide study

摘要: Background Lowering low-density lipoprotein cholesterol with statin therapy results in substantial reductions cardiovascular events, and larger may produce benefits. In rare cases, myopathy occurs association therapy, especially when the statins are administered at higher doses certain other medications. Methods We carried out a genomewide study using approximately 300,000 markers (and additional fine-mapping) 85 subjects definite or incipient 90 controls, all of whom were taking 80 mg simvastatin daily as part trial involving 12,000 participants. Replication was tested 40 20,000 Results The scan yielded single strong rs4363657 single-nucleotide polymorphism (SNP) located within SLCO1B1 on chromosome 12 (P=4x10(-9)). encodes organic anion-transporting polypeptide OATP1B1, which has been shown to regulate hepatic uptake statins. noncoding SNP nearly complete linkage disequilibrium nonsynonymous rs4149056 (r(2)=0.97), linked metabolism. prevalence C allele population 15%. odds ratio for 4.5 (95% confidence interval [CI], 2.6 7.7) per copy allele, 16.9 CI, 4.7 61.1) CC compared TT homozygotes. More than 60% these cases could be attributed variant. replicated daily, also showed an between cholesterol-lowering effects simvastatin. No SNPs any region clearly associated myopathy. Conclusions have identified common variants that strongly increased risk statin-induced Genotyping help achieve benefits more safely effectively. (Current Controlled Trials number, ISRCTN74348595.)