engleski

Pharmacogenetics and statin-related myopathy: what do we know?

The article presents the most important clinically relevant findings on the pharmacogenetics of statins. Despite the clear benefits for many patients, concerns and controversies exist around statin adverse effects including diabetes mellitus, hepatotoxicity, cognitive impairment and particularly musculoskeletal symptoms. Multiple genes that affect statin pharmacokinetics have been studied, including metabolizing enzymes CYP3A4, CYP3A5 and CYP2C9 ; UGT1A1, UGT1A3 and UGT2B7) and transporters. OATP1B1 transporter pivotal to the hepatic uptake of most statins. OATP1B1 is encoded by the gene, SLCO1B1. A variant (rs4149056, c.521T> ; C, p.V174A) within SLCO1B1 has been identified and replicated in numerous unbiased genome-wide association studies as the strongest genomic association with simvastatin- induced myotoxicity. A genotype dose-response relationship exists with the odds ratio of myopathy on simvastatin 80 mg being 4.5 (95% CI: 2.6–7.7) in rs4149056 T heterozygotes and 16.9 (95% CI: 4.7–61.1) among CC homozygotes compared with TT (wild-type) homozygotes. Beyond simvastatin, SLCO1B1 rs4149056 has been associated with increased systemic exposure to all statins except fluvastatin, albeit to a lower extent than simvastatin.

statins ; simvastatin ; OATP1B1 ; SLCO1B1 ; myopathy

nije evidentirano