title: Association between ABCB1 genotype and seizure outcome in Collies with epilepsy.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  Heterogeneity of the ABCB1 gene is associated with seizure outcome in dogs with epilepsy.
  
  
  METHODS
  Twenty-nine Collies with epilepsy being treated with antiepileptic drugs (AEDs).
  
  
  METHODS
  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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA. Karen_Munana@ncsu.edu
authors.forename: K R
authors.initials: KR
authors.lastname: Muñana
authors.forename: J A
authors.initials: JA
authors.lastname: Nettifee-Osborne
authors.forename: R L
authors.initials: RL
authors.lastname: Bergman
authors.forename: K L
authors.initials: KL
authors.lastname: Mealey
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001965:Bromides / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy / Q000235:genetics*; D004285:Dogs; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D010634:Phenobarbital / Q000627:therapeutic use
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D001965:Bromides; D010634:Phenobarbital