Wafaa Moustafa M Abo El Fotoh1, Sameh Abd Allah Abd El Naby2, Mona Salah El-Din Habib3, Abeer Ahmed ALrefai4, Zeinab A Kasemy5. 1. Lecturer of Pediatrics, Faculty of Medicine, Menoufia University Hospital, Egypt. Electronic address: wafaamoustafa60@yahoo.com. 2. Lecturer of Pediatrics, Faculty of Medicine, Menoufia University Hospital, Egypt. Electronic address: samehabdallah75@yahoo.com. 3. Lecturer of Medical Biochemistry, Faculty of Medicine, Menoufia University Hospital, Egypt. Electronic address: elhosam4545@yahoo.com. 4. Lecturer of Medical Biochemistry, Faculty of Medicine, Menoufia University, Egypt. Electronic address: drabeer1975@hotmail.com. 5. Lecturer of Public Health and Community Medicine, Faculty of Medicine, Menoufia University, Egypt. Electronic address: nanokas@yahoo.com.
Abstract
PURPOSE: 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.
PURPOSE: 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 SCN1Ac.3184 A/G (rs2298771) and CYP3A5*3 (rs776746) polymorphisms could serve as genetic based biomarkers to predict pharmacoresistance among Egyptian epilepticchildren. METHODS: Genotyping of SCN1Ac.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 epilepticpatients 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 SCN1Ac.3184 A/G polymorphism in epilepsy and moreover in development of pharmacoresistance among Egyptian epilepticchildren. CYP3A5*3 variants have no contributing effect on pharmacoresistance among Egyptian epilepticchildren.