Association ofSLCO1B1c.521T > C (rs4149056) with discontinuation of atorvastatin due to statin-associated muscle symptoms

摘要

The most common adverse drug reaction from statins are statin-associated muscle symptoms (SAMS), characterized by myopathy (weakness), myalgia (muscle pain), and commonly elevation in serum creatine kinase. All statins are substrates of the organic anion transporter 1B1 (OATP1B1; gene:SLCO1B1), albeit to different degrees. A genetic polymorphism inSLCO1B1, c.521T>C (rs4149056), markedly decreases OATP1B1 function. The literature is currently unclear as to whetherSLCO1B1c.521T>C is significantly associated with discontinuation of atorvastatin specifically due to SAMS. Our hypothesis was that individuals carrying theSLCO1B1decreased function 521C allele are more likely to discontinue atorvastatin due to SAMS. This was a retrospective analysis of survey data from 379 Caucasians genotyped for rs4149056 and treated with atorvastatin for at least 12 months. Crude and multivariable logistic regression, adjusted for established risk factors for SAMS, determined the association ofSLCO1B1c.521T>C with discontinuation of atorvastatin due to SAMS (SLCO1B1521T-homozygotes vs. 521C-carriers). The sample was 51% male, with a mean age of 57 years (SD = 11). Sixty-one percent of participants reported discontinuing atorvastatin due to SAMS, and 32% overall carried the 521C allele.SLCO1B1521C-carrier status was not a significant predictor of atorvastatin discontinuation in any model: crude OR = 1.07; 95% CI, 0.68-1.66;P = 0.78 and adjusted OR = 1.07; 95% CI, 0.68-1.69;P = 0.76. The results were similar in a sub-group of participants treated with higher doses of atorvastatin (>20 mg). In summary,SLCO1B1c.521T>C was not significantly associated with discontinuation of atorvastatin therapy due to SAMS.