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Challenges and recommendations for conducting epidemiological studies in the field of epilepsy pharmacogenetics

Epilepsy is one of the most prevalent neurological disorders, afflicting approximately 50 million Indians. Owing to affordability and easy availability, use of first-generation antiepileptic drugs (AEDs) is heavily encouraged for the treatment of epilepsy in resource-limited countries such as India....

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Autores principales: Grover, Sandeep, Gupta, Meenal, Kukreti, Ritushree
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125045/
https://www.ncbi.nlm.nih.gov/pubmed/21747586
http://dx.doi.org/10.4103/0971-6866.80351
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author Grover, Sandeep
Gupta, Meenal
Kukreti, Ritushree
author_facet Grover, Sandeep
Gupta, Meenal
Kukreti, Ritushree
author_sort Grover, Sandeep
collection PubMed
description Epilepsy is one of the most prevalent neurological disorders, afflicting approximately 50 million Indians. Owing to affordability and easy availability, use of first-generation antiepileptic drugs (AEDs) is heavily encouraged for the treatment of epilepsy in resource-limited countries such as India. Although first-generation AEDs are at par with second-generation AEDs in terms of efficacy, adverse drug reactions (ADRs) are quite common with them. This could be attributed to the inferior pharmacokinetic parameters such as nonlinear metabolism, narrow therapeutic index and formation of toxic intermediates. In addition, epilepsy patients may differ in the pharmacokinetic and pharmacodynamic profiles, with about 1/3(rd) of the population failing to respond to treatment. A proportion of this interindividual variability in response may be explained by genetic heterogeneity in the activity and expression of the network of proteins such as metabolizing enzymes, transporters and targets of AEDs. Over the last two decades, a considerable effort has been made by the scientific community for unraveling this genetic basis of variable response to AEDs. However, there have been inconsistencies in such genetic association studies conducted across different territories of the world. There could be several reasons underlying the poor replicability of these studies, mainly nonuniform phenotypic definitions, poor sample size and interethnic variability. In the present review article, we provide an overview of heterogeneity in study designs for conducting pharmacogenetic studies. In addition, critical recommendations required for overcoming such challenges imposed by pharmacogenetic epidemiological studies have been briefly discussed.
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spelling pubmed-31250452011-07-11 Challenges and recommendations for conducting epidemiological studies in the field of epilepsy pharmacogenetics Grover, Sandeep Gupta, Meenal Kukreti, Ritushree Indian J Hum Genet Review Article Epilepsy is one of the most prevalent neurological disorders, afflicting approximately 50 million Indians. Owing to affordability and easy availability, use of first-generation antiepileptic drugs (AEDs) is heavily encouraged for the treatment of epilepsy in resource-limited countries such as India. Although first-generation AEDs are at par with second-generation AEDs in terms of efficacy, adverse drug reactions (ADRs) are quite common with them. This could be attributed to the inferior pharmacokinetic parameters such as nonlinear metabolism, narrow therapeutic index and formation of toxic intermediates. In addition, epilepsy patients may differ in the pharmacokinetic and pharmacodynamic profiles, with about 1/3(rd) of the population failing to respond to treatment. A proportion of this interindividual variability in response may be explained by genetic heterogeneity in the activity and expression of the network of proteins such as metabolizing enzymes, transporters and targets of AEDs. Over the last two decades, a considerable effort has been made by the scientific community for unraveling this genetic basis of variable response to AEDs. However, there have been inconsistencies in such genetic association studies conducted across different territories of the world. There could be several reasons underlying the poor replicability of these studies, mainly nonuniform phenotypic definitions, poor sample size and interethnic variability. In the present review article, we provide an overview of heterogeneity in study designs for conducting pharmacogenetic studies. In addition, critical recommendations required for overcoming such challenges imposed by pharmacogenetic epidemiological studies have been briefly discussed. Medknow Publications 2011-05 /pmc/articles/PMC3125045/ /pubmed/21747586 http://dx.doi.org/10.4103/0971-6866.80351 Text en © Indian Journal of Human Genetics http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Grover, Sandeep
Gupta, Meenal
Kukreti, Ritushree
Challenges and recommendations for conducting epidemiological studies in the field of epilepsy pharmacogenetics
title Challenges and recommendations for conducting epidemiological studies in the field of epilepsy pharmacogenetics
title_full Challenges and recommendations for conducting epidemiological studies in the field of epilepsy pharmacogenetics
title_fullStr Challenges and recommendations for conducting epidemiological studies in the field of epilepsy pharmacogenetics
title_full_unstemmed Challenges and recommendations for conducting epidemiological studies in the field of epilepsy pharmacogenetics
title_short Challenges and recommendations for conducting epidemiological studies in the field of epilepsy pharmacogenetics
title_sort challenges and recommendations for conducting epidemiological studies in the field of epilepsy pharmacogenetics
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125045/
https://www.ncbi.nlm.nih.gov/pubmed/21747586
http://dx.doi.org/10.4103/0971-6866.80351
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