Genetic association analysis of transporters identifies ABCC2 loci for seizure control in women with epilepsy on first-line antiepileptic drugs

Pharmacogenetics and Genomics
Sandeep GroverRitushree Kukreti

Abstract

The ATP-binding cassette (ABC) superfamily of transporters is known to efflux antiepileptic drugs (AEDs) primarily in the brain, gastrointestinal tract, liver, and kidneys. In addition, they are also known to be involved in estrogen disposition and may modulate seizure susceptibility and drug response. The objective of the present study was to investigate the role of genetic variants from ABC transporters in seizure control in epilepsy patients treated with monotherapy of first-line AEDs for 12 months. On the basis of gene coverage and functional significance, a total of 98 single nucleotide polymorphisms from ABCB1, ABCC1, and ABCC2 were genotyped in 400 patients from North India. Of these, 216 patients were eligible for therapeutic assessment. Genetic variants were compared between the 'no-seizures' and the 'recurrent-seizures' groups. Bonferroni corrections for multiple comparisons and adjustment for covariates were performed before assessment of associations. Functionally relevant promoter polymorphisms from ABCC2: c.-1549G>A and c.-1019A>G either considered alone or in haplotype and diplotype combinations were observed for a significant association with seizure control in women (odds ratio>3.5, P<10, power>95%). Further, l...Continue Reading

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Citations

Apr 6, 2013·Pharmacogenomics·Ingolf CascorbiSilke Vogelgesang
Aug 8, 2013·CNS Neuroscience & Therapeutics·Harpreet KaurRitushree Kukreti
Nov 7, 2016·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Long QianZhi-Cheng Gong
Jun 9, 2017·Pharmacogenomics·Hazel Xiaohui AngMichael D Winther
Apr 4, 2021·Viruses·Ingrid Fricke-Galindo, Ramcés Falfán-Valencia

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