Association of Genetic Polymorphism of Gene ABCB1 with Statin resistance in cardiac patients from the tertiary care hospital of South Punjab, Pakistan

Abstract

The present study aimed to determine the frequency distribution and association of genetic polymorphism with statin treatment in the population of Punjab, Pakistan. Atorvastatin therapy is associated with ABCB1 (ATP-binding cassette transporter) gene expression and LDL cholesterol reduction. Two common SNPs, rs2032582, rs1045642 of the ABCB1 gene, were selected, variants of which are associated with muscle toxicity. The hypothesis that there is a significant association between single nucleotide polymorphism (SNP) at 3435 T>C and 2677 G>A/T of the gene ABCB1 that affects statin therapy in cardiac patients of the tertiary care hospital of Punjab, Pakistan. Methods. For this,100 cardiac patients with percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS) who were undergoing treatment with statin (Atorvastatin) were selected. Lipid profile was determined using a commercial assay kit. The patients were analyzed for rs2032582 and rs1045642 allelic variants using an allele-specific primer extension polymerase chain reaction method followed by sequencing to confirm the mutation. The results were expressed in mean ± SEM, and in all cases, the difference was considered significant when p<0.05.Results. The present results showed allele variant AC at SNP rs1045642 (3435 T>C) showed a significant increase in total cholesterol (p = 0.05), reduction in HDL (p=0.02), and increase in TG (p = 0.01), while a significant increase (p=0.042) in cholesterol was found in the CT variant. And, variants (AC, AT, CT) at SNP rs2032582 (2677 G>A/T) of ABCB1 showed a significant increase in TGs (P= 0.04, p=0.03, p= 0.008, respectively) and total cholesterol (p=0.02, p=0.04, p=0.04, respectively) with the increase in LDL cholesterol in AC (p =0.012) and AT (p=0.016). These results were found to be concordant with the chromatograms obtained by sequencing.

Conclusion: The failure of drug response and resistance draws the conclusion that not only single nucleotide polymorphism but epigenetic factors and other enzymes with transcriptional and translational factors are also responsible for the metabolism and side effects of Atorvastatin.