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

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 model...

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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
id 2-s2.0-84961762798
spelling 2-s2.0-84961762798
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.
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
2016
Journal of Pharmacy and Pharmaceutical Sciences
19
1
10.18433/J38G7X
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84961762798&doi=10.18433%2fJ38G7X&partnerID=40&md5=0aa9ba3460c8df8691191864ad1bf729
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.
Canadian Society for Pharmaceutical Sciences
14821826
English
Article
All Open Access; Gold Open Access
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.
spellingShingle 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.
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
author_facet 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.
author_sort 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.
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publishDate 2016
container_title Journal of Pharmacy and Pharmaceutical Sciences
container_volume 19
container_issue 1
doi_str_mv 10.18433/J38G7X
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-84961762798&doi=10.18433%2fJ38G7X&partnerID=40&md5=0aa9ba3460c8df8691191864ad1bf729
description 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.
publisher Canadian Society for Pharmaceutical Sciences
issn 14821826
language English
format Article
accesstype All Open Access; Gold Open Access
record_format scopus
collection Scopus
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