Coupling genotyping and computational modeling in prediction of antiepileptic drugs that cause Stevens Johnson syndrome and toxic epidermal Necrolysis for carrier of HLA-B*15:02

• Published in: Journal of Pharmacy and Pharmaceutical Sciences
• Main Author: Teh L.K.; Selvaraj M.; Bannur Z.; Ismail M.I.M.; Rafia M.H.; Law W.C.; Sapuan S.; Puvanarajah S.; Ali P.S.S.; Salleh M.Z.
• Format: Article
• Language: English
• Published: Canadian Society for Pharmaceutical Sciences 2016
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-84961762798&doi=10.18433%2fJ38G7X&partnerID=40&md5=0aa9ba3460c8df8691191864ad1bf729
• ISSN: 14821826
• DOI: 10.18433/J38G7X

Purpose. The importance of HLA-B*15:02 genotyping to avoid carbamazepine induced SJS/TEN and molecular modeling to predict the role of HLA-B*15:0 and AEDs induced SJS/TEN are investigated. Methods. DNA was extracted from eighty-six patients. The patients were genotyped by AS-PCR. Computational modeling of the HLA-B*15:02 followed by docking studies were performed to screen 26 AEDs that may induce ADR among HLA-B*15:02 carriers. Results. Odd ratio for CBZ induced SJS/TEN and HLAB* 15:02 was 609.0 (95% CI: 23-15873; p=0.0002). Molecular modeling studies showed that acetazolamide, ethosuxiamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone and sodium-valproate may induce ADR in HLA-B*15:02 carriers alike CBZ. Conclusion. We confirmed HLA-B*15:02 as a predictor of SJS/TEN and recommend pre-screening. Computational prediction of DIHR is useful in personalized medicine. © 2016, Canadian Society for Pharmaceutical Sciences. All rights reserved.