Molecular Genetics of Drug-resistance in Epilepsies.
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Date
2014-01
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Abstract
Nearly one-third of newly diagnosed patients with epilepsy remain unresponsive to
antiepileptic drugs (AEDs), etiopathogenesis of which is poorly understood. The genes
encoding the proteins that regulate the pharmacokinetics such as P-glycoprotein
[ABCBI], major vault protein [MVP gene] and drug metabolizing enzymes [ABCB1,
ABCG2, MVP, CYP2C9, CYP2C19, CYP3A4, CYP3A5, EPHX1, UGT1A1, UGT2B7],
and pharmacodynamics such as sodium channels [SCN1A, SCN2A] and GABA
receptors [GABRA1, GABRA6, GABRB2, GABRG2] of AEDs are under intense
investigation to unravel the mysteries of AED-resistance. However, till today, a
consistent and reliable result that could help the clinician either to predict drugresistance
or to overcome it has not been forthcoming. The discrepant results may be
related to variations in the definition of drug-resistance, heterogeneous patient
populations, ethnic variations in the frequency distribution of single nucleotide
polymorphisms (SNPs) and the selection of SNPs. Understanding of these limitations
of existing studies, hopefully, will help in designing better studies.
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Radhakrishnan Kurupath. Molecular Genetics of Drug-resistance in Epilepsies. Annals of the National Academy of Medical Sciences (India). 2014 Jan-June; 50(1&2): 6-19.