The Association Between Polymorphisms in RLIP76 and Drug Response in Epilepsy
Abstract
Introduction Approximately 30% of patients with epilepsy are resistant to treatment with anti-epileptic drugs (AEDs). The ABC drug transporter proteins are hypothesized to mediate drug resistance in epilepsy. More recently, a non-ABC putative transporter, RLIP76, has also been proposed to be involved in the mechanism of pharmacoresistance. One previous association study of six polymorphisms in RLIP76 failed to find any association with drug resistance in a retrospective cohort of epilepsy patients. We aimed to look for an association with outcomes reflecting drug response in a larger prospective cohort, with gene-wide coverage. Patients and methods We investigated the role of common polymorphisms in RLIP76 in epilepsy pharmacoresistance by genotyping 23 common RLIP76 polymorphisms in a prospective cohort of 503 epilepsy patients, from the standard and new anti-epileptic drugs (SANAD) prospective study of new and old AEDs. A total of 13 of these were tested for association with four outcomes reflecting response to drugs: time to first seizure, time to 12-month remission, time to withdrawal due to inadequate seizure control, and time to withdrawal due to unacceptable adverse drug events. Results No significant associations, allowing for multiple testing, were found in the whole cohort. There was also no effect in a subgroup of patients on carbamazepine, which is thought to be a RLIP76 substrate, although two polymorphisms were associated with time to first seizure (p = 0.007).…
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In 503 UK epilepsy patients genotyped for 23 common Rlip polymorphisms, 16 polymorphisms were found, of which three had a frequency of less than 1%.
“Leschziner et al. (2007) genotyped 503 UK epilepsy patients for 23 common Rlip polymorphisms. Among these patients they found 16 polymorphisms, of which three had a frequency of less than 1%.”
From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [114]
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Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease?
Hindle, A., Singh, S. P., Pradeepkiran, J. A., Bose, C., Vijayan, M., Kshirsagar, S., Sawant, N. A., & Reddy, P. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116098 · Cited by 14 · see citing works
- Authors
- Leschziner, G. D., Jorgensen, A. L., Andrew, T., Williamson, P. R., Marson, A. G., Coffey, A. J., Middleditch, C., Balding, D. J., Rogers, J., Bentley, D. R., Chadwick, D., Johnson, M. R., & Pirmohamed, M.
- Affiliations
- Wellcome Sanger Institute (GB)
- University of Liverpool (GB)
- Imperial College London (GB)
- Walton Centre (GB)
- ORCID
- Venue
- Pharmacogenomics
- Publisher
- Informa UK Limited
- Published
- 2007-12
- Volume
- 8
- Issue
- 12
- Pages
- 1715-1722
- ISSN
- 1462-2416 (ISSN-L)
- 1744-8042
- OpenAlex
- W1983282754
- Cited by
- 18
- References
- 0
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2016: 1 · 2013: 2
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacogenomics (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- UK Department of Health “Health Technology Assessment” programme
- Neurology Entry/Exit Scholarship from the Guarantors of Brain
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- RLIP76, epilepsy, antiepileptic drugs, drug resistance, pharmacoresistance, genetic polymorphism, drug-gene interactions, carbamazepine, ABC transporters, seizure control, adverse drug reactions, time to remission
- MeSH terms
- Adult, Aged, Drug Resistance, Epilepsy, Female, Genotype, Humans, Male, Middle Aged, ATP-Binding Cassette Transporters, Polymorphism, Single Nucleotide, GTPase-Activating Proteins
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