Impact of SLCO1B1 and ABCB1 variants on statin efficacy and toxicity in a Tunisian population

Statins are the cornerstone treatment for coronary artery disease treatment. However, they exhibit considerable interindividual variability in both pharmacokinetics and pharmacodynamics. This variability was assessed by investigating 9 genetic variants impact across 5 pharmacogenes (ABCB1, CYP3A4, CETP, APOC1, and SLCO1B1) in 279 Tunisian coronary patients newly started on statins. Regarding myopathy, carrying the variant allele G of SLCO1B1 rs2306283 reduced myopathy risk (odds ratio [OR] = 0.322, P = .008) compared with a allele. Conversely, the variant allele C of SLCO1B1 rs4149056 appeared to increase myopathy occurrence (OR = 4.799, P = .001) compared with T allele. Stratifying by statin type, the associations were only significant for atorvastatin, not for rosuvastatin, with a protective effect for rs2306283 (OR = 0.502, P = .046) and at risk of rs4149056 (OR = 4.290, P = .003). Sex analysis revealed no significant differences between sexes and safety for rs4149056. However, for rs2306283, the protective effect was more pronounced in men (OR = 0.348, P = .015) compared with women. Concerning efficacy, the variant alleles C of ABCB1 rs1045642 and rs1128503 were found to be significantly associated with nonresponse to statins for both low density lipoprotein cholesterol (LDL-c; OR = 0.350, P = .023 and OR = 0.292, P = .011, respectively) and non-high-density lipoprotein cholesterol (non-HDL-c; OR = 0.302, P = .007 and OR = 0.200, P = .002, respectively) compared with T allele. Stratifying by statin type, the association was only significant with atorvastatin, not with rosuvastatin, for both LDL-c (rs1045642, OR = 0.331, P = .013 and rs1128503, OR = 0.249, P = .004), and non-HDL-c (rs1045642, OR = 0.363, P = .011 and rs1128503, OR = 0.207, P = .001). Sex analysis revealed significant association between efficacy and ABCB1 only in men, for both LDL-c (rs1045642, OR = 0.355, P = .013 and rs1128503, OR = 0.325, P = .012), and non-HDL-c (rs1045642, OR = 0.272, P = .001 and rs1128503, OR = 0.400, P = .023). Our findings substantiate the clinical utility of genetic biomarkers in predicting statins response. SIGNIFICANCE STATEMENT: Although statins remain a cornerstone therapy for acute coronary syndromes, significant interindividual variability in efficacy and toxicity exists. These findings suggest that SLCO1B1 variants may influence the occurrence of statin-induced myopathy, whereas ABCB1 polymorphisms may affect statin efficacy. This highlights the potential of pharmacogenetic screening to optimize the benefit-risk balance of statin therapy.