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Genetic analysis of CYP2D6 polymorphism in Indian populations and its pharmacogenetic implications
journal contribution
posted on 2016-07-01, 10:17 authored by Shamima Choudhury, Liz AkamLiz Akam, Sarabjit MastanaSarabjit MastanaDespite 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.
History
School
- Sport, Exercise and Health Sciences
Published in
Current Pharmacogenomics and Personalized MedicineVolume
12Issue
2Pages
123 - 132Citation
CHOUDHURY, S., AKAM, E.C. and MASTANA, S.S., 2014. Genetic analysis of CYP2D6 polymorphism in Indian populations and its pharmacogenetic implications. Current Pharmacogenomics and Personalized Medicine, 12(2), pp. 123-132.Publisher
© Bentham ScienceVersion
- VoR (Version of Record)
Publisher statement
This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/Publication date
2014Notes
This paper is in closed access.ISSN
1875-6921Publisher version
Language
- en