Impact of CYP3A4 rs2242480 polymorphisms on Imatinib HPLC determined trough concentration and response in Chronic Myeloid Leukaemia in Pakistani patients

Abstract

Objective To ascertain the impact of CYP3A4 polymorphism on the therapeutic outcome of imatinib and its trough concentration Study design Descriptive analytical study Place and duration of the study This study was conducted in the Department of Pharmacology & Therapeutics, Islamic International Medical College, between December 2020 and February 2022, in collaboration with the Institute of Biomedical Genetic Engineering, KRL Hospital Islamabad. Methods Patients with Chronic Myeloid Leukaemia age range–18-70 years were included in this study. One group comprised responders and the other group comprised non-responders. Imatinib trough levels in both groups were determined using High-performance Liquid Chromatography and compared, and the association was determined with therapeutic outcomes. DNA was extracted, and the PCR restriction fragment length polymorphism technique was used to identify the alleles. The results were analyzed using Statistical Package for Social Sciences (SPSS) version 22.0. Results The imatinib concentration in patients with the homozygous wild allele CC of rs2242480 was higher(1298ng/ml) as compared with the mutant homozygous TT allele (489ng/ml) or heterozygous allele CT(873ng/ml) Conclusion There was a significant association between imatinib trough levels and CYP3A4 polymorphism, and trough concentration was found to be lower in patients with the TT or CT variant of rs2242480 than in patients with the CC genotype.