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

Lay Kek Teh, Manikandan Selvaraj, Zakaria Bannur, Mohd Ikhwan Mohd Ismail, Md Hanip Rafia, Wan Chung Law, Sapiah Sapuan, Santhi Puvanarajah, Pakeer Shaik Syed Ali, Mohd Zaki Salleh

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)147-160
Number of pages14
JournalJournal of Pharmacy and Pharmaceutical Sciences
Volume19
Issue number1
DOIs
Publication statusPublished - 24 Mar 2016
Externally publishedYes

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