Farhad Kamali
Newcastle upon Tyne, United Kingdom.
Title: Effect of genetic, patient and clinical factors on statin-related myotoxicity
Biography
Biography: Farhad Kamali
Abstract
Although statins are generally well-tolerated, statin associated musculoskeletal symptoms (SAMS) are relatively common. True statin-related myotoxicity (SRM) is much less common and rhabdomyolysis, the severest consequence of myopathy, is a rare event. Genetic factors associated with enhanced statin systemic exposure and muscular availability increase the risk of severe myopathy; however it is not clear whether the same or different genetic factors operate across the spectrum of SRM from myalgia to milder myopathy, as encountered in routine practice. The current study examined associations between clinical and genetic factors and SRM in a case-control design study in patients at high cardiovascular risk. 120 SRM cases (who discontinued statins due to intolerable statin related muscle symptoms) and 481 statin tolerant controls (treated with either 40 mg simvastatin or 80 mg atorvastatin daily) were studied. The association between 12 single nucleotide polymorphisms (SNPs) in nine candidate genes [i.e., SLCO1B1, ABCC2, ABCG2, CYP3A4, COQ2, glycine amidinotransferase (GATM), glutathione peroxidases 1 and 4 (GPX1 and GPX4), SLC16A1, SLC16A3] and patient factors (age, sex, BMI, comorbidities and concurrent therapy) with SRM was evaluated. Of the 12 SNPs genotyped, only rs4149056 in SLCO1B1 was associated with SRM (P = 0.031, P = 0.014 in univariate and binary logistic regression analysis, respectively) with odds ratio of 1.60 (95 % CI= 1.05-2.45) and this association was influenced by sex (P= 0.006). In multivariate logistic regression analyses of data only SLCO1B1 rs4149056 genotype (OR=1.72, 95% CI: 1.15- 2.59, P=0.014) and sex (OR=1.72, 95% CI =1.15 - 2.59, P=0.006) were independently associated with SRM. We conclude that genetic factors associated with statin systemic exposure are implicated in the full spectrum of SRM. However among the genetic variants studied here, only SLCO1B1 rs4149056 warrants further evaluation for the identification of patients who may be susceptible to myopathy.