Genetic abnormality of cytochrome-P2C9*3 allele predisposes to epilepsy and phenytoin-induced adverse drug reactions: genotyping findings of cytochrome-alleles in the North Indian population
Abstract Background This research aims to study the association of genetic polymorphism in genes coding for CYP2C9 and CYP2C19 in phenytoin-induced dose-related toxicity and to assess if the presence of allele CYP2C9*3 plays a role in phenytoin-induced idiosyncratic adverse effects. Current observat...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2022-10-01
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| Series: | Future Journal of Pharmaceutical Sciences |
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| Online Access: | https://doi.org/10.1186/s43094-022-00432-6 |
| _version_ | 1811335375154577408 |
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| author | Vivek Kumar Garg Supriya Ritu Shree Ajay Prakash Aastha Takkar Madhu Khullar Biman Saikia Bikash Medhi Manish Modi |
| author_facet | Vivek Kumar Garg Supriya Ritu Shree Ajay Prakash Aastha Takkar Madhu Khullar Biman Saikia Bikash Medhi Manish Modi |
| author_sort | Vivek Kumar Garg |
| collection | DOAJ |
| description | Abstract Background This research aims to study the association of genetic polymorphism in genes coding for CYP2C9 and CYP2C19 in phenytoin-induced dose-related toxicity and to assess if the presence of allele CYP2C9*3 plays a role in phenytoin-induced idiosyncratic adverse effects. Current observational case control study included 142 patients with phenytoin-induced adverse drug reactions (ADRs) and 100 controls. All these patients underwent genotyping to determine the type of CYP2C9 allele [CYP2C9*1, CYP2C9*2 or CYP2C9*3) and CYP2C19 allele (CYP2C19*1, CYP2C19*2 or CYP2C19*3] by real-time polymerase chain reaction (RT-PCR) using Applied Biosystems (ABI) 7500 Real-Time PCR System (USA). Results Presence of homozygous status for allele CYP2C9*3 was associated with significantly higher risk of phenytoin-induced dose-dependent ADRs, dose-independent ADRs, gum hyperplasia, and skin rash. Presence of heterozygous status for allele CYP2C9*3 was associated with significantly higher risk of phyenytoin-induced dose-dependent ADRs and dose-independent ADRs. Presence of either heterozygous or homozygous status for CYP2C9*2 and CYP2C19*2 did not have any bearing on dose-related side effects. None of the patients showed CYP2C19*3 allele. Conclusion Variant alleles of CYP2C9*3 are significantly overexpressed among patients with phenytoin-induced ADRs, thereby suggesting the role for CYP2C9 genotype testing to predict risk of phenytoin-related ADRs. |
| first_indexed | 2024-04-13T17:23:11Z |
| format | Article |
| id | doaj.art-6b0479331eb34a37b86e82aa0a41699d |
| institution | Directory Open Access Journal |
| issn | 2314-7253 |
| language | English |
| last_indexed | 2024-04-13T17:23:11Z |
| publishDate | 2022-10-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Future Journal of Pharmaceutical Sciences |
| spelling | doaj.art-6b0479331eb34a37b86e82aa0a41699d2022-12-22T02:37:54ZengSpringerOpenFuture Journal of Pharmaceutical Sciences2314-72532022-10-01811810.1186/s43094-022-00432-6Genetic abnormality of cytochrome-P2C9*3 allele predisposes to epilepsy and phenytoin-induced adverse drug reactions: genotyping findings of cytochrome-alleles in the North Indian populationVivek Kumar Garg0Supriya1Ritu Shree2Ajay Prakash3Aastha Takkar4Madhu Khullar5Biman Saikia6Bikash Medhi7Manish Modi8Postgraduate Institute of Medical Education and ResearchPostgraduate Institute of Medical Education and ResearchPostgraduate Institute of Medical Education and ResearchPostgraduate Institute of Medical Education and ResearchPostgraduate Institute of Medical Education and ResearchPostgraduate Institute of Medical Education and ResearchPostgraduate Institute of Medical Education and ResearchPostgraduate Institute of Medical Education and ResearchPostgraduate Institute of Medical Education and ResearchAbstract Background This research aims to study the association of genetic polymorphism in genes coding for CYP2C9 and CYP2C19 in phenytoin-induced dose-related toxicity and to assess if the presence of allele CYP2C9*3 plays a role in phenytoin-induced idiosyncratic adverse effects. Current observational case control study included 142 patients with phenytoin-induced adverse drug reactions (ADRs) and 100 controls. All these patients underwent genotyping to determine the type of CYP2C9 allele [CYP2C9*1, CYP2C9*2 or CYP2C9*3) and CYP2C19 allele (CYP2C19*1, CYP2C19*2 or CYP2C19*3] by real-time polymerase chain reaction (RT-PCR) using Applied Biosystems (ABI) 7500 Real-Time PCR System (USA). Results Presence of homozygous status for allele CYP2C9*3 was associated with significantly higher risk of phenytoin-induced dose-dependent ADRs, dose-independent ADRs, gum hyperplasia, and skin rash. Presence of heterozygous status for allele CYP2C9*3 was associated with significantly higher risk of phyenytoin-induced dose-dependent ADRs and dose-independent ADRs. Presence of either heterozygous or homozygous status for CYP2C9*2 and CYP2C19*2 did not have any bearing on dose-related side effects. None of the patients showed CYP2C19*3 allele. Conclusion Variant alleles of CYP2C9*3 are significantly overexpressed among patients with phenytoin-induced ADRs, thereby suggesting the role for CYP2C9 genotype testing to predict risk of phenytoin-related ADRs.https://doi.org/10.1186/s43094-022-00432-6EpilepsyCYP2C9PhenytoinAdverse drug reaction |
| spellingShingle | Vivek Kumar Garg Supriya Ritu Shree Ajay Prakash Aastha Takkar Madhu Khullar Biman Saikia Bikash Medhi Manish Modi Genetic abnormality of cytochrome-P2C9*3 allele predisposes to epilepsy and phenytoin-induced adverse drug reactions: genotyping findings of cytochrome-alleles in the North Indian population Future Journal of Pharmaceutical Sciences Epilepsy CYP2C9 Phenytoin Adverse drug reaction |
| title | Genetic abnormality of cytochrome-P2C9*3 allele predisposes to epilepsy and phenytoin-induced adverse drug reactions: genotyping findings of cytochrome-alleles in the North Indian population |
| title_full | Genetic abnormality of cytochrome-P2C9*3 allele predisposes to epilepsy and phenytoin-induced adverse drug reactions: genotyping findings of cytochrome-alleles in the North Indian population |
| title_fullStr | Genetic abnormality of cytochrome-P2C9*3 allele predisposes to epilepsy and phenytoin-induced adverse drug reactions: genotyping findings of cytochrome-alleles in the North Indian population |
| title_full_unstemmed | Genetic abnormality of cytochrome-P2C9*3 allele predisposes to epilepsy and phenytoin-induced adverse drug reactions: genotyping findings of cytochrome-alleles in the North Indian population |
| title_short | Genetic abnormality of cytochrome-P2C9*3 allele predisposes to epilepsy and phenytoin-induced adverse drug reactions: genotyping findings of cytochrome-alleles in the North Indian population |
| title_sort | genetic abnormality of cytochrome p2c9 3 allele predisposes to epilepsy and phenytoin induced adverse drug reactions genotyping findings of cytochrome alleles in the north indian population |
| topic | Epilepsy CYP2C9 Phenytoin Adverse drug reaction |
| url | https://doi.org/10.1186/s43094-022-00432-6 |
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