Pharmacodynamic and cytogenetic evaluation in CYP2C19*2 and CYP2C19*3 allelomorphism in South Indian population with clopidogrel therapy

Abstract

BackgroundGenetic factors play a significant role in pathogenesis of most diseases of heart. The present study was undertaken to correlate coronary artery disease with demographical, biochemical alterations, SNPs, gene expression and chromosomal abnormalities and for further enlightening the investigation in this field. Methods150 patients taking clopidogrel drug were selected and single nucleotide polymorphism was done by PCR-RFLP techniques. With the same patients cytogenetic analysis was carried out on leukocyte cultures by karyotyping. Gene expression studies for 20 CAD patients and normal controls were done by RT-PCR techniques. ResultsIn this study of patients with coronary artery disease the frequencies of the Extreme Metabolizers, Intermediate Metabolizers in CYP2C19*2 (rs4244285) were present in 90% and 10% but no Poor Metabolizers were found in this allele. The frequencies of Extreme Metabolizer, Intermediate Metabolizer and Poor Metabolizer in CYP2C19*3 (rs4986893) were present in 41%, 50% and 9% respectively. Among 20 CAD samples, 13 of 20 (65%) showed CYP2C19 gene over expression in CAD patients and all controls showed normal expression. Among the 150 CAD patients, 145 had normal karyotype, only five patients showed change in normal karyogram carried out by leukocyte culture. ConclusionGenetic testing of CYP2C19 may help in prescribing a dose according to genetic makeup and represent the initial steps towards the development of diagnostic tests and therapeutic strategies that will substantially improve human health. This study highlights the progress that has been made in using pharmacogenomic and gene expression analysis, cardiovascular genomic research and the potential for applying these findings in clinical medicine.