title: Association of ABCB1 genetic variants 3435C>T and 2677G>T to ABCB1 mRNA and protein expression in brain tissue from refractory epilepsy patients.
abstract: OBJECTIVE
  There is evidence from studies in rodents that P-glycoprotein (P-gp) overexpression is implicated in the causation of refractory epilepsy. Genetic variants in the human ABCB1 (MDR1) gene were shown to affect the expression levels of the transporter in various tissues and to be associated with refractory epilepsy. However, the effect of the genetic variants on the P-gp level in epileptogenic brain tissue is poorly investigated. In the present study, we examined the impact of putatively functional polymorphisms 3435C>T and 2677G>T in the ABCB1 gene on the ABCB1 mRNA expression and P-gp content in human brain tissue from epileptogenic foci of the patients with refractory epilepsy.
  
  
  METHODS
  Fresh brain tissue specimens were obtained from therapy-refractory epilepsy patients during neurosurgery of the epileptogenic focus. We determined the ABCB1 mRNA expression in 23 samples using 5' exonuclease-based real-time polymerase chain reaction (PCR) as well as the P-gp content in 32 samples determined by immunohistochemistry, genotyping was performed by PCR/restriction fragment length polymorphism (RFLP).
  
  
  RESULTS
  There was lack of association of 3435C>T and 2677G>T as well as diplotype configurations on ABCB1 mRNA expression and P-gp content in epileptogenic brain tissues.
  
  
  CONCLUSIONS
  We cannot exclude an association of ABCB1 variants on P-gp function, but our results suggest that brain ABCB1 mRNA and protein expression is not substantially influenced by major ABCB1 genetic variants thus explaining in part results from case-control studies obtaining lack of association of ABCB1 polymorphisms to the risk of refractory epilepsy.
authors.affiliation: Institute of Pharmacology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Mosyagin
authors.forename: Uwe
authors.initials: U
authors.lastname: Runge
authors.forename: Henry W
authors.initials: HW
authors.lastname: Schroeder
authors.forename: Eike
authors.initials: E
authors.lastname: Dazert
authors.forename: Silke
authors.initials: S
authors.lastname: Vogelgesang
authors.forename: Werner
authors.initials: W
authors.lastname: Siegmund
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Warzok
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D000906:Antibodies; D000927:Anticonvulsants / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004351:Drug Resistance; D004727:Endothelium / Q000276:immunology / Q000378:metabolism; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000906:Antibodies; D000927:Anticonvulsants; D012333:RNA, Messenger