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Indian Journal of Human Genetics
Medknow Publications on behalf of Indian Society of Human Genetics
ISSN: 0971-6866
EISSN: 0971-6866
Vol. 17, No. s1, 2011, pp. 12-21
Bioline Code: hg11058
Full paper language: English
Document type: Review Article
Document available free of charge

Indian Journal of Human Genetics, Vol. 17, No. s1, 2011, pp. 12-21

 en Drug resistance in epilepsy and the ABCB1 gene: The clinical perspective
Das, Abhijit.; Balan, Shabeesh.; Banerjee, Moinak. & Radhakrishnan, Kurupath.


Multidrug resistance is one of the most serious problems in the treatment of epilepsy that is likely to have a complex genetic and acquired basis. Various experimental data support the hypothesis that over-expression of antiepileptic drug (AED) transporters may play a pivotal role in drug resistance. However, key questions concerning their functionality remain unanswered. The idea that P-glycoprotein, encoded by the ABCB1 gene, might mediate at least part of the drug resistance was met with both enthusiasm and skepticism. As in oncology, initial optimism has been clouded subsequently by conflicting results. The first study reporting a positive association between genetic variation in the P-glycoprotein and multidrug-resistant epilepsy was published in 2003. Since then, several other genetic association studies have attempted to verify this result. However, taken overall, the role of P-glycoprotein in drug resistance in epilepsy still remains uncertain. We intend to critically review the inherent problems associated with epilepsy pharmacogenetic studies in general and with ABCB1 polymorphisms studies in particular. The lessons learnt from the ABCB1 studies can help us to guide future association genetics studies to investigate AED resistance, and thereby taking us closer to the cherished dream of personalized AED therapy.

ABCB1, antiepileptic drugs, drug resistance, epilepsy, genetic association studies, genome-wide association studies, P-glycoprotein, single nucleotide polymorphism

© Copyright 2011 Indian Journal of Human Genetics.
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