title: Polymorphisms in the ABCB1 gene in phenobarbital responsive and resistant idiopathic epileptic Border Collies.
abstract: BACKGROUND
  Variation in the ABCB1 gene is believed to play a role in drug resistance in epilepsy.
  
  
  OBJECTIVE
  Variation in the ABCB1 gene encoding the permeability-glycoprotein could have an influence on phenobarbital (PB) resistance, which occurs with high frequency in idiopathic epileptic Border Collies (BCs).
  
  
  METHODS
  Two hundred and thirty-six client-owned BCs from Switzerland and Germany including 25 with idiopathic epilepsy, of which 13 were resistant to PB treatment.
  
  
  METHODS
  Prospective and retrospective case-control study. Data were collected retrospectively regarding disease status, antiepileptic drug (AED) therapy, and drug responsiveness. The frequency of a known mutation in the ABCB1 gene (4 base-pair deletion in the ABCB1 gene [c.296_299del]) was determined in all BCs. Additionally, the ABCB1 coding exons and flanking sequences were completely sequenced to search for additional variation in 41 BCs. Association analyses were performed in 2 case-control studies: idiopathic epileptic and control BCs and PB-responsive and resistant idiopathic epileptic BCs.
  
  
  RESULTS
  One of 236 BCs (0.4%) was heterozygous for the mutation in the ABCB1 gene (c.296_299del). A total of 23 variations were identified in the ABCB1 gene: 4 in exons and 19 in introns. The G-allele of the c.-6-180T > G variation in intron 1 was significantly more frequent in epileptic BCs resistant to PB treatment than in epileptic BCs responsive to PB treatment (P(raw) = .0025).
  
  
  CONCLUSIONS
  A variation in intron 1 of the ABCB1 gene is associated with drug responsiveness in BCs. This might indicate that regulatory mutations affecting the expression level of ABCB1 could exist, which may influence the reaction of a dog to AEDs.
authors.affiliation: Department of Clinical Veterinary Medicine, Division of Clinical Neurology, Vetsuisse Faculty, University of Bern, Switzerland. lisa.alves@itn.unibe.ch
authors.forename: L
authors.initials: L
authors.lastname: Alves
authors.forename: V
authors.initials: V
authors.lastname: Hülsmeyer
authors.forename: A
authors.initials: A
authors.lastname: Jaggy
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: T
authors.initials: T
authors.lastname: Leeb
authors.forename: M
authors.initials: M
authors.lastname: Drögemüller
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy / Q000235:genetics*; D004285:Dogs; D004351:Drug Resistance / Q000235:genetics; D004831:Epilepsies, Myoclonic / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D005786:Gene Expression Regulation; D010634:Phenobarbital / Q000627:therapeutic use*; D011110:Polymorphism, Genetic
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D010634:Phenobarbital