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Cytochrome P(450) 2D6 polymorphism in eastern Indian population

OBJECTIVES: Cytochrome P(450) 2D6 (CYP2D6) enzyme metabolizes a quarter of prescription drugs. Polymorphisms of CYP2D6 gene and resultant phenotypic variations in metabolic activity have been described in various populations. We assessed the prevalence of CYP2D6 activity phenotypes, employing dextro...

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Autores principales: Dhuya, Monalisa, Pal, Murari Mohan, Hazra, Avijit, Chatterjee, Suparna, Gogtay, Nithya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer - Medknow 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446679/
https://www.ncbi.nlm.nih.gov/pubmed/32874001
http://dx.doi.org/10.4103/ijp.IJP_530_17
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author Dhuya, Monalisa
Pal, Murari Mohan
Hazra, Avijit
Chatterjee, Suparna
Gogtay, Nithya
author_facet Dhuya, Monalisa
Pal, Murari Mohan
Hazra, Avijit
Chatterjee, Suparna
Gogtay, Nithya
author_sort Dhuya, Monalisa
collection PubMed
description OBJECTIVES: Cytochrome P(450) 2D6 (CYP2D6) enzyme metabolizes a quarter of prescription drugs. Polymorphisms of CYP2D6 gene and resultant phenotypic variations in metabolic activity have been described in various populations. We assessed the prevalence of CYP2D6 activity phenotypes, employing dextromethorphan (DXM) as probe drug in subjects with at least two parental generations residing in eastern India. MATERIALS AND METHODS: Unrelated healthy subjects took 60 mg DXM after fasting overnight. Blood samples were collected 3 h after dosing and plasma separated. DXM and its primary metabolite dextrorphan (DXT) were measured by liquid chromatography with tandem mass spectrometry. The DXM-to-DXT metabolic ratio (MR) was obtained for each subject. Histogram of MR values suggested bimodal distribution. A polynomial regression equation derived through probit analysis was solved to identify the antimode of the MR values. Subjects with log(MR) < antimode were extensive metabolizers (EMs). Log(MR) ≥ antimode indicated poor metabolizers (PMs). RESULTS: We evaluated the results from 97 participants. The median MR was 0.209 (interquartile range: 0.090–0.609), while the antimode for MR was 3.055. From these, it was inferred that three subjects were PMs, while the rest were EMs. CYP2D6 polymorphism prevalence is low (3.09%; 95% confidence interval: 0.35%–6.54%) in the population of eastern India and matches the prevalence in other zones of the country. CONCLUSIONS: Differences in CYP2D6 activity has treatment implications and may lead to adverse events or therapeutic failure. Phenotyping of subjects receiving CYP2D6 metabolized drugs may help clinicians personalize treatment and avert adverse drug-drug interactions. However, the frequency of the PM phenotype is low in India, and routinely phenotyping for CYP2D6 activity will not be cost-effective. We cannot recommend it at this stage.
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spelling pubmed-74466792020-08-31 Cytochrome P(450) 2D6 polymorphism in eastern Indian population Dhuya, Monalisa Pal, Murari Mohan Hazra, Avijit Chatterjee, Suparna Gogtay, Nithya Indian J Pharmacol Research Article OBJECTIVES: Cytochrome P(450) 2D6 (CYP2D6) enzyme metabolizes a quarter of prescription drugs. Polymorphisms of CYP2D6 gene and resultant phenotypic variations in metabolic activity have been described in various populations. We assessed the prevalence of CYP2D6 activity phenotypes, employing dextromethorphan (DXM) as probe drug in subjects with at least two parental generations residing in eastern India. MATERIALS AND METHODS: Unrelated healthy subjects took 60 mg DXM after fasting overnight. Blood samples were collected 3 h after dosing and plasma separated. DXM and its primary metabolite dextrorphan (DXT) were measured by liquid chromatography with tandem mass spectrometry. The DXM-to-DXT metabolic ratio (MR) was obtained for each subject. Histogram of MR values suggested bimodal distribution. A polynomial regression equation derived through probit analysis was solved to identify the antimode of the MR values. Subjects with log(MR) < antimode were extensive metabolizers (EMs). Log(MR) ≥ antimode indicated poor metabolizers (PMs). RESULTS: We evaluated the results from 97 participants. The median MR was 0.209 (interquartile range: 0.090–0.609), while the antimode for MR was 3.055. From these, it was inferred that three subjects were PMs, while the rest were EMs. CYP2D6 polymorphism prevalence is low (3.09%; 95% confidence interval: 0.35%–6.54%) in the population of eastern India and matches the prevalence in other zones of the country. CONCLUSIONS: Differences in CYP2D6 activity has treatment implications and may lead to adverse events or therapeutic failure. Phenotyping of subjects receiving CYP2D6 metabolized drugs may help clinicians personalize treatment and avert adverse drug-drug interactions. However, the frequency of the PM phenotype is low in India, and routinely phenotyping for CYP2D6 activity will not be cost-effective. We cannot recommend it at this stage. Wolters Kluwer - Medknow 2020 2020-08-04 /pmc/articles/PMC7446679/ /pubmed/32874001 http://dx.doi.org/10.4103/ijp.IJP_530_17 Text en Copyright: © 2020 Indian Journal of Pharmacology http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
spellingShingle Research Article
Dhuya, Monalisa
Pal, Murari Mohan
Hazra, Avijit
Chatterjee, Suparna
Gogtay, Nithya
Cytochrome P(450) 2D6 polymorphism in eastern Indian population
title Cytochrome P(450) 2D6 polymorphism in eastern Indian population
title_full Cytochrome P(450) 2D6 polymorphism in eastern Indian population
title_fullStr Cytochrome P(450) 2D6 polymorphism in eastern Indian population
title_full_unstemmed Cytochrome P(450) 2D6 polymorphism in eastern Indian population
title_short Cytochrome P(450) 2D6 polymorphism in eastern Indian population
title_sort cytochrome p(450) 2d6 polymorphism in eastern indian population
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446679/
https://www.ncbi.nlm.nih.gov/pubmed/32874001
http://dx.doi.org/10.4103/ijp.IJP_530_17
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