title: The potential implication of SCN1A and CYP3A5 genetic variants on antiepileptic drug resistance among Egyptian epileptic children.
abstract: OBJECTIVE
  Despite the advances in the pharmacological treatment of epilepsy, pharmacoresistance still remains challenging. Understanding of the pharmacogenetic causes is critical to predict drug response hence providing a basis for personalized medications. Genetic alteration in activity of drug target and drug metabolizing proteins could explain the development of pharmacoresistant epilepsy. So the aim of this study was to explore whether SCN1A c.3184 A/G (rs2298771) and CYP3A5*3 (rs776746) polymorphisms could serve as genetic based biomarkers to predict pharmacoresistance among Egyptian epileptic children.
  
  
  METHODS
  Genotyping of SCN1A c.3184 A/G and CYP3A5*3 polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed in 65 healthy control subjects and 130 patients with epilepsy, of whom 50 were drug resistant and 80 were drug responsive.
  
  
  RESULTS
  There was a significant higher frequency of the AG genotype (p=0.001) and G allele (p=0.006) of SCN1A polymorphism in epileptic patients than in controls. Also their frequency was significantly higher in drug resistant patients in comparison with drug responders (p=0.005 and 0.054 respectively). No significant association between CYP3A5*3 polymorphism and drug-resistance was found.
  
  
  CONCLUSIONS
  Overall, results confirmed the claimed role of SCN1A c.3184 A/G polymorphism in epilepsy and moreover in development of pharmacoresistance among Egyptian epileptic children. CYP3A5*3 variants have no contributing effect on pharmacoresistance among Egyptian epileptic children.
authors: Lecturer of Pediatrics, Faculty of Medicine, Menoufia University Hospital, Egypt. Electronic address: wafaamoustafa60@yahoo.com.
authors: Wafaa Moustafa M
authors: WM
authors: Abo El Fotoh
authors: Lecturer of Pediatrics, Faculty of Medicine, Menoufia University Hospital, Egypt. Electronic address: samehabdallah75@yahoo.com.
authors: Sameh Abd Allah
authors: SA
authors: Abd El Naby
authors: Lecturer of Medical Biochemistry, Faculty of Medicine, Menoufia University Hospital, Egypt. Electronic address: elhosam4545@yahoo.com.
authors: Mona Salah El-Din
authors: MS
authors: Habib
authors: Lecturer of Medical Biochemistry, Faculty of Medicine, Menoufia University, Egypt. Electronic address: drabeer1975@hotmail.com.
authors: Abeer Ahmed
authors: AA
authors: ALrefai
authors: Lecturer of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Egypt. Electronic address: nanokas@yahoo.com.
authors: Zeinab A
authors: ZA
authors: Kasemy
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D000069279:Drug Resistant Epilepsy / Q000235:genetics*; D004534:Egypt; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018709:Statistics, Nonparametric
chemical_list: D000927:Anticonvulsants; D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human; D051544:Cytochrome P-450 CYP3A
keywords: CYP3A5*3; Drug-resistant; Epilepsy; Genetic polymorphisms; SCN1A