The association between the c.521T>C variant allele in SLCO1B1 (reference single nucleotide polymorphism (rs)4149056) and
simvastatin-induced
myotoxicity was discovered over a decade ago; however, whether this relationship represents a class effect is still not fully known. The aim of this study was to investigate the relationship between rs4149056 genotype and
statin-induced
myotoxicity in patients taking
atorvastatin and
lovastatin. Study participants were from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. A total of 233
statin-induced
myopathy +
rhabdomyolysis cases met the criteria for inclusion and were matched to 2,342 controls. To validate the
drug response phenotype, we replicated the previously established association between rs4149056 genotype and
simvastatin-induced
myotoxicity. In particular, compared with homozygous T allele carriers, there was a significantly increased risk of
simvastatin-induced myopathy + rhabdomyolysis in homozygous carriers of the C allele (CC vs. TT, odds ratio [OR] 4.62, 95% confidence interval [CI] 1.58-11.90, P = 0.003). For
lovastatin users, homozygous carriers of the C allele were also at increased risk of
statin-induced myopathy + rhabdomyolysis (CC vs. TT, OR 4.49, 95% CI 1.68-10.80, P = 0.001). In
atorvastatin users, homozygous carriers of the C allele were twice as likely to experience
statin-induced
myopathy, though this association did not achieve statistical significance (CC vs. TT, OR 2.00, 95% CI 0.44-6.59, P = 0.30). In summary, our findings suggest that the association of rs4149056 with
simvastatin-related
myotoxicity may also extend to
lovastatin. More data is needed to determine the extent of the association in
atorvastatin users. Altogether, these data expand the evidence base for informing guidelines of pharmacogenetic-based
statin prescribing practices.