SLCO1B1 RS2306283 (C.388A>G) POLYMORPHISM IS ASSOCIATED WITH ALTERED RESPONSE TO ATORVASTATIN IN PATIENTS WITH METABOLIC SYNDROME

Background: Organic anion transporting polypeptide 1B1 (OATP1B1), encoded by the SLCO1B1 gene, plays an important role in hepatic uptake of atorvastatin. Genetic polymorphisms in SLCO1B1 may alter atorvastatin response. Objective: To assess the association of SLCO1B1 rs2306283 (c.388A>G) polymorphism with lipid lowering response to atorvastatin in patients with metabolic syndrome (MetS) attending a tertiary care center in North India. Methods: A total of 121 patients were screened, of whom 91 eligible patients were enrolled. Eighty patients completed the 8-week follow-up and were included in final analysis. Newly diagnosed patients with MetS received atorvastatin 20 mg once daily for 8 weeks. Genotyping for SLCO1B1 rs2306283 polymorphism was performed using PCR-RFLP technique. Lipid parameters and surrogate cardiovascular risk markers were compared among different genotypic variants. Results: Genotype frequencies for AA, AG and GG variants were 25%, 35% and 40%, respectively. Allelic frequencies for A and G alleles were 42.5% and 57.5%, respectively. Patients with GG genotype demonstrated significantly greater increase in HDL cholesterol levels and greater reduction in LDL cholesterol levels after 8 weeks of atorvastatin therapy compared to AA genotype (p<0.05). Significant improvement was also observed in surrogate cardiovascular risk markers including non-HDL cholesterol, cardiac risk ratio, atherogenic coefficient and atherogenic index of plasma in patients carrying G allele. Conclusion: SLCO1B1 rs2306283 (c.388A>G) polymorphism was associated with altered lipid lowering response to atorvastatin in patients with MetS. Presence of G allele was associated with better therapeutic response to atorvastatin. Further large multicentric studies are required to validate these findings.