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Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy

BACKGROUND: Phenytoin, mainly metabolized by cytochrome P450 enzyme system, has a narrow therapeutic index and may have adverse effects due to inter-individual variation in the dose requirement and genetic polymorphisms. This cross-sectional study was done to study the prevalence of cytochrome P450...

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Autores principales: Chaudhary, Nagendra, Kabra, Madhulika, Gulati, Sheffali, Gupta, Yogendra Kumar, Pandey, Ravindra Mohan, Bhatia, Bal Dev
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868001/
https://www.ncbi.nlm.nih.gov/pubmed/27179628
http://dx.doi.org/10.1186/s12887-016-0603-0
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author Chaudhary, Nagendra
Kabra, Madhulika
Gulati, Sheffali
Gupta, Yogendra Kumar
Pandey, Ravindra Mohan
Bhatia, Bal Dev
author_facet Chaudhary, Nagendra
Kabra, Madhulika
Gulati, Sheffali
Gupta, Yogendra Kumar
Pandey, Ravindra Mohan
Bhatia, Bal Dev
author_sort Chaudhary, Nagendra
collection PubMed
description BACKGROUND: Phenytoin, mainly metabolized by cytochrome P450 enzyme system, has a narrow therapeutic index and may have adverse effects due to inter-individual variation in the dose requirement and genetic polymorphisms. This cross-sectional study was done to study the prevalence of cytochrome P450 CYP2C9 polymorphisms in Indian epileptic children and to see the effect of polymorphisms on serum levels in epileptic children on phenytoin monotherapy. METHODS: We studied 89 epileptic children of North Indian population, randomly selected, to see the genotypic and allelic frequency of CYP2C9 and its association with drug levels on phenytoin monotherapy. Analysis was done using STATA 9 Software. The results were analyzed as prevalence at 95 % C.I. (Confidence Interval). The difference in mean phenytoin serum levels between wild and mutant alleles was tested using Student`s T test for independent samples. P value less than 0.05 was considered statistically significant. RESULTS: CYP2C9*1, *2 & *3 allelic frequencies were 85.4, 4.5 and 10.1 % respectively. CYP2C9*3 allelic group showed significantly higher serum phenytoin levels compared to the wild variants (P = 0.009). There was no statistically significant difference in the dose received (P = 0.12) and side effects of CYP2C9*2 and CYP2C9*3 genotypes (P = 0.442 and 0.597 respectively) when compared with wild variant. CONCLUSION: CYP2C9*3 is more common than *2 in the present study. All the polymorphisms demonstrated in our study were heterozygous with no homozygosity. Serum phenytoin levels are higher in polymorphic groups (*3) which suggest their poor metabolizing nature. Genotyping may help to avoid toxicity and concentration-dependent adverse effects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12887-016-0603-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-48680012016-05-17 Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy Chaudhary, Nagendra Kabra, Madhulika Gulati, Sheffali Gupta, Yogendra Kumar Pandey, Ravindra Mohan Bhatia, Bal Dev BMC Pediatr Research Article BACKGROUND: Phenytoin, mainly metabolized by cytochrome P450 enzyme system, has a narrow therapeutic index and may have adverse effects due to inter-individual variation in the dose requirement and genetic polymorphisms. This cross-sectional study was done to study the prevalence of cytochrome P450 CYP2C9 polymorphisms in Indian epileptic children and to see the effect of polymorphisms on serum levels in epileptic children on phenytoin monotherapy. METHODS: We studied 89 epileptic children of North Indian population, randomly selected, to see the genotypic and allelic frequency of CYP2C9 and its association with drug levels on phenytoin monotherapy. Analysis was done using STATA 9 Software. The results were analyzed as prevalence at 95 % C.I. (Confidence Interval). The difference in mean phenytoin serum levels between wild and mutant alleles was tested using Student`s T test for independent samples. P value less than 0.05 was considered statistically significant. RESULTS: CYP2C9*1, *2 & *3 allelic frequencies were 85.4, 4.5 and 10.1 % respectively. CYP2C9*3 allelic group showed significantly higher serum phenytoin levels compared to the wild variants (P = 0.009). There was no statistically significant difference in the dose received (P = 0.12) and side effects of CYP2C9*2 and CYP2C9*3 genotypes (P = 0.442 and 0.597 respectively) when compared with wild variant. CONCLUSION: CYP2C9*3 is more common than *2 in the present study. All the polymorphisms demonstrated in our study were heterozygous with no homozygosity. Serum phenytoin levels are higher in polymorphic groups (*3) which suggest their poor metabolizing nature. Genotyping may help to avoid toxicity and concentration-dependent adverse effects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12887-016-0603-0) contains supplementary material, which is available to authorized users. BioMed Central 2016-05-14 /pmc/articles/PMC4868001/ /pubmed/27179628 http://dx.doi.org/10.1186/s12887-016-0603-0 Text en © Chaudhary et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Chaudhary, Nagendra
Kabra, Madhulika
Gulati, Sheffali
Gupta, Yogendra Kumar
Pandey, Ravindra Mohan
Bhatia, Bal Dev
Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy
title Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy
title_full Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy
title_fullStr Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy
title_full_unstemmed Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy
title_short Frequencies of CYP2C9 polymorphisms in North Indian population and their association with drug levels in children on phenytoin monotherapy
title_sort frequencies of cyp2c9 polymorphisms in north indian population and their association with drug levels in children on phenytoin monotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868001/
https://www.ncbi.nlm.nih.gov/pubmed/27179628
http://dx.doi.org/10.1186/s12887-016-0603-0
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