{"title":"Impact of <i>ABCB1</i> genetic polymorphism on carbamazepine dose requirement among Southern Indian persons with epilepsy.","authors":"Elango Dhivya, Ramasamy Kesavan, Nair P Pradeep","doi":"10.1515/dmpt-2023-0054","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Carbamazepine (CBZ) is one of the oldest, yet first line drugs for treating epilepsy. However, there is a large inter-individual difference in requirement of maintenance dose and one third of persons treated with antiepileptic drugs (AEDs) exhibit drug resistance to therapy. One of the proposed mechanisms for the drug resistance was increased expression of efflux transporter P-glycoprotein. The pharmacogenetic studies of drug transporters (<i>ABCB1</i>) done in combination therapies of AEDs were inconclusive. Hence, we have attempted to study the impact of <i>ABCB1 3435C>T</i> genetic polymorphism and CBZ monotherapy in persons with epilepsy (PWE) from South India, which is a genetically distinct population<b>.</b> With this background, this study was aimed to determine the dose of CBZ in <i>ABCB1 3435C>T</i> genotypes and to determine the distribution of <i>ABCB1 3435C>T</i> genotypes (which codes P-glycoprotein) between responders and non-responders to CBZ therapy.</p><p><strong>Methods: </strong>A cross sectional study was conducted in 200 persons with epilepsy, who were categorised as responders and non-responders according to ILAE (international league against epilepsy) criteria. Eligible participants were enrolled from the epilepsy clinic of the neurology department and five ml of blood was collected. DNA extraction and genotyping were done by phenol-chloroform method and real time polymerase chain reaction (RT-PCR), respectively.</p><p><strong>Results: </strong>The mean maintenance dose of carbamazepine was statistically significant among different genotypes (p<0.05) of <i>ABCB1 3435C>T</i> (526 vs. 637 mg/day in CC vs. TT genotype). There was no significant association between <i>ABCB1 3435C>T</i> polymorphism (p=0.827) and CBZ resistance in PWE. Duration of disease and age of onset were found to be significant in predicting the response to CBZ therapy.</p><p><strong>Conclusions: </strong>We report that <i>ABCB1 3435C>T</i> polymorphism is significantly associated with an increase in dose requirement of CBZ in persons with epilepsy from South India.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug metabolism and personalized therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/dmpt-2023-0054","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: Carbamazepine (CBZ) is one of the oldest, yet first line drugs for treating epilepsy. However, there is a large inter-individual difference in requirement of maintenance dose and one third of persons treated with antiepileptic drugs (AEDs) exhibit drug resistance to therapy. One of the proposed mechanisms for the drug resistance was increased expression of efflux transporter P-glycoprotein. The pharmacogenetic studies of drug transporters (ABCB1) done in combination therapies of AEDs were inconclusive. Hence, we have attempted to study the impact of ABCB1 3435C>T genetic polymorphism and CBZ monotherapy in persons with epilepsy (PWE) from South India, which is a genetically distinct population. With this background, this study was aimed to determine the dose of CBZ in ABCB1 3435C>T genotypes and to determine the distribution of ABCB1 3435C>T genotypes (which codes P-glycoprotein) between responders and non-responders to CBZ therapy.
Methods: A cross sectional study was conducted in 200 persons with epilepsy, who were categorised as responders and non-responders according to ILAE (international league against epilepsy) criteria. Eligible participants were enrolled from the epilepsy clinic of the neurology department and five ml of blood was collected. DNA extraction and genotyping were done by phenol-chloroform method and real time polymerase chain reaction (RT-PCR), respectively.
Results: The mean maintenance dose of carbamazepine was statistically significant among different genotypes (p<0.05) of ABCB1 3435C>T (526 vs. 637 mg/day in CC vs. TT genotype). There was no significant association between ABCB1 3435C>T polymorphism (p=0.827) and CBZ resistance in PWE. Duration of disease and age of onset were found to be significant in predicting the response to CBZ therapy.
Conclusions: We report that ABCB1 3435C>T polymorphism is significantly associated with an increase in dose requirement of CBZ in persons with epilepsy from South India.
期刊介绍：
Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.
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