title: Relationship between ABCB1 3435TT genotype and antiepileptic drugs resistance in Epilepsy: updated systematic review and meta-analysis.
abstract: BACKGROUND
  Antiepileptic drugs (AEDs) are effective medications available for epilepsy. However, many patients do not respond to this treatment and become resistant. Genetic polymorphisms may be involved in the variation of AEDs response. Therefore, we conducted an updated systematic review and a meta-analysis to investigate the contribution of the genetic profile on epilepsy drug resistance.
  
  
  METHODS
  We proceeded to the selection of eligible studies related to the associations of polymorphisms with resistance to AEDs therapy in epilepsy, published from January 1980 until November 2016, using Pubmed and Cochrane Library databases. The association analysis was based on pooled odds ratios (ORs) and 95% confidence intervals (CIs).
  
  
  RESULTS
  From 640 articles, we retained 13 articles to evaluate the relationship between ATP-binding cassette sub-family C member 1 (ABCB1) C3435T polymorphism and AEDs responsiveness in a total of 454 epileptic AEDs-resistant cases and 282 AEDs-responsive cases. We found a significant association with an OR of 1.877, 95% CI 1.213-2.905. Subanalysis by genotype model showed a more significant association between the recessive model of ABCB1 C3435T polymorphism (TT vs. CC) and the risk of AEDs resistance with an OR of 2.375, 95% CI 1.775-3.178 than in the dominant one (CC vs. TT) with an OR of 1.686, 95% CI 0.877-3.242.
  
  
  CONCLUSIONS
  Our results indicate that ABCB1 C3435T polymorphism, especially TT genotype, plays an important role in refractory epilepsy. As genetic screening of this genotype may be useful to predict AEDs response before starting the treatment, further investigations should validate the association.
authors.affiliation: Department of Genetic, Tunis El Manar University, Faculty of Medicine of Tunis, 15 Jebel Lakhdhar street, La Rabta, 1007, Tunis, Tunisia. chch.m@hotmail.fr.|Department of Child Neurology, National Institute Mongi Ben Hmida of Neurology, UR12SP24 Abnormal Movements of Neurologic Diseases, Jebel Lakhdhar street, La Rabta, 1007, Tunis, Tunisia. chch.m@hotmail.fr.
authors.forename: Malek
authors.initials: M
authors.lastname: Chouchi
authors.affiliation: Division of Histology and Immunology Division, Department of Basic Sciences, Faculty of Medicine of Tunis, 15 Jebel Lakhdhar street, La Rabta, 1007, Tunis, Tunisia.
authors.forename: Wajih
authors.initials: W
authors.lastname: Kaabachi
authors.affiliation: Department of Child Neurology, National Institute Mongi Ben Hmida of Neurology, UR12SP24 Abnormal Movements of Neurologic Diseases, Jebel Lakhdhar street, La Rabta, 1007, Tunis, Tunisia.
authors.forename: Hedia
authors.initials: H
authors.lastname: Klaa
authors.affiliation: Division of Histology and Immunology Division, Department of Basic Sciences, Faculty of Medicine of Tunis, 15 Jebel Lakhdhar street, La Rabta, 1007, Tunis, Tunisia.
authors.forename: Kalthoum
authors.initials: K
authors.lastname: Tizaoui
authors.affiliation: Department of Child Neurology, National Institute Mongi Ben Hmida of Neurology, UR12SP24 Abnormal Movements of Neurologic Diseases, Jebel Lakhdhar street, La Rabta, 1007, Tunis, Tunisia.
authors.forename: Ilhem Ben-Youssef
authors.initials: IB
authors.lastname: Turki
authors.affiliation: Department of Genetic, Faculty of Medicine of Tunis, 15 Jebel Lakhdhar street, La Rabta, 1007, Tunis, Tunisia.
authors.forename: Lamia
authors.initials: L
authors.lastname: Hila
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use*; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000927:Anticonvulsants
keywords: ABCB1 C3435T polymorphism; Antiepileptic drugs; Epilepsy; Meta-analysis; Resistance