Findings from this study were presented at the 2010 American College of Veterinary Internal Medicine Forum, Anaheim, CA, June 2010.
Association between ABCB1 Genotype and Seizure Outcome in Collies with Epilepsy
Article first published online: 24 SEP 2012
Copyright © 2012 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 26, Issue 6, pages 1358–1364, November/December 2012
How to Cite
Muñana, K.R., Nettifee-Osborne, J.A., Bergman, R.L. and Mealey, K.L. (2012), Association between ABCB1 Genotype and Seizure Outcome in Collies with Epilepsy. Journal of Veterinary Internal Medicine, 26: 1358–1364. doi: 10.1111/j.1939-1676.2012.01006.x
- Issue published online: 20 NOV 2012
- Article first published online: 24 SEP 2012
- Manuscript Accepted: 15 AUG 2012
- Manuscript Revised: 13 JUN 2012
- Manuscript Received: 25 FEB 2012
- Collie Health Foundation and North Carolina State University Department of Clinical Sciences
- Antiepileptic drug;
- Drug resistance;
Medically refractory seizures are an important problem in both humans and dogs with epilepsy. Altered expression of ABCB1, the gene encoding for p-glycoprotein (PGP), has been proposed to play a role in drug-resistant epilepsy.
Heterogeneity of the ABCB1 gene is associated with seizure outcome in dogs with epilepsy.
Twenty-nine Collies with epilepsy being treated with antiepileptic drugs (AEDs).
Prospective and retrospective cohort study. Dogs were classified as having a good outcome (≤1 seizure/month, no cluster seizures) or a poor outcome (>1 seizure/month, with or without cluster seizures) based on owner-completed questionnaire. Serum AED concentrations were measured, and ABCB1 genotyping was performed on buccal tissue samples. Association analyses were performed for genotype and seizure outcome, number of AEDs administered, serum AED concentrations, and incidence of adverse effects.
Fourteen dogs of 29 (48%) were homozygous for the ABCB1-1∆ mutation (M/M), 11 dogs (38%) were heterozygous (M/N), and 4 dogs (14%) had the wild-type genotype (N/N). Dogs with the M/M genotype were significantly more likely to have fewer seizures and have less AED-related sedation than M/N or N/N dogs (P = .003 and P = .001, respectively). Serum phenobarbital and bromide concentrations did not differ between groups, but the M/N and N/N groups received a larger number of AEDs than the M/M group (P = .014).
Conclusions and Clinical Importance
ABCB1 genotype is associated with seizure outcome in Collies with epilepsy. This cannot be attributed to differences in PGP function, but might be because of intrinsic variations in seizure severity among phenotypes.