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Manna , Jose and Moinak, Banerjee and Anila , Mathew and Tashi , Bharadwaj and Neetha , Vijayan (2014) Pharmacogenetic evaluation of ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase polymorphisms in teratogenicity of anti-epileptic drugs in women with epilepsy. Annals of Indian Academy of Neurology, 17 (3). pp. 259-266. ISSN 1998-3549

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Abstract

Pregnancy in women with epilepsy (WWE) who are on anti-epileptic drugs (AEDs) has two- to three-fold increased risk of fetal malformations. AEDs are mostly metabolized by Cyp2C9, Cyp2C19 and Cyp3A4 and transported by ABCB1. Patients on AED therapy can have folate deficiency. We hypothesize that the polymorphisms in ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase (MTHFR) might result in differential expression resulting in differential drug transport, drug metabolism and folate metabolism, which in turn may contribute to the teratogenic impact of AEDs. MATERIALS AND METHODS: The ABCB1, Cyp2C9, Cyp2C19 and MTHFR polymorphisms were genotyped for their role in teratogenic potential and the nature of teratogenecity in response to AED treatment in WWE. The allelic, genotypic associations were tested in 266 WWE comprising of 143 WWE who had given birth to babies with WWE-malformation (WWE-M) and 123 WWE who had normal offsprings (WWE-N). RESULTS: In WWE-M, CC genotype of Ex07 + 139C/T was overrepresented (P = 0.0032) whereas the poor metabolizer allele *2 and *2 *2 genotype of CYP2C219 was significantly higher in comparison to WWE-N group (P = 0.007 and P = 0.005, respectively). All these observations were independent of the nature of malformation (cardiac vs. non cardiac malformations). CONCLUSION: Our study indicates the possibility that ABCB1 and Cyp2C19 may play a pivotal role in the AED induced teratogenesis, which is independent of nature of malformation. This is one of the first reports indicating the pharmacogenetic role of Cyp2C19 and ABCB1 in teratogenesis of AED in pregnant WWE.

Item Type: Article
Uncontrolled Keywords: ABCB1, anti-epileptic drugs, Cyp2C19, Cyp2C9, epilepsy, methylene tetrahydrofolate reductase, pharmacogenomics, South India, teratogenic
Subjects: Human Molecular Genetics
Depositing User: Rgcb Library
Date Deposited: 17 Jul 2017 08:07
Last Modified: 17 Jul 2017 08:07
URI: http://rgcb.sciencecentral.in/id/eprint/406

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