Genetic analysis of CYP2D6 polymorphism in Indian populations and its pharmacogenetic implications

Abstract

Despite the rapid development of pharmacogenetic testing and the frequencies of medication related emergencies increasing, pharmacogentic testing is not yet implemented extensively in clinical practice. Several studies document that polymorphic Cytochrome P450 isoenzymes CYP2C9, CYP2C19 and CYP2D6 are responsible for the metabolism of many clinically important drugs and xenobiotics. These polymorphisms contribute to inter-individual and interethnic variation in drug metabolism which may lead to differences in drug response, suggesting that common dose regimen will not always equivocate to efficacious dosing. The CYP2D6*2, CYP2D6*4 and CYP2D6*10 variants were studied in four Indian populations (Gujarati, Punjabi, Bengali and Koya tribe). Genotypes at individual alleles were identified using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Differences in frequencies of CYP2D6 genotypes/ alleles were compared at regional and global level. CYP2D6*2 variant frequency was highest among Gujarati population (47%) Gujarati and Punjabi populations showed high levels of CYP2D6*4 (13% and 24% respectively), whilst high levels of CYP2D6*10 were found in Bengali and Koya populations (21% and 12% respectively). At genotypic level, CYP2D6 *4/*4 genotype was absent in all study populations, resulting in the absence of the PM (poor metaboliser) phenotype in these samples. Overall there are significant differences among Indian populations at this locus. Overall observed allele frequency spectrum fits well into other Indian and European populations. There are significant differences in CYP2D6 allele and genotype frequencies in 4 populations leading to differential estimates of EM and IM. These results suggest the importance of delivering pharmacotherapeutic regimes for patients on the basis of their genetic profile.