Open AccessCoupling Genotyping and Computational Modeling in Prediction of Anti-epileptic Drugs that cause Stevens Johnson Syndrome and Toxic Epidermal Necrolysis for Carrier of HLA-B*15:02
Author(s) -
Lay Kek Teh,
Manikandan Selvaraj,
Zakaria Bannur,
Mohd Ikhwan Mohd Ismail,
Hanip Rafia,
Wan Chung Law,
Sapiah Sapuan,
Santhi Datuk Puvanarajah,
Pakeer Shaik Syed Ali,
Mohd Zaki Salleh
Publication year - 2016
Publication title -
journal of pharmacy and pharmaceutical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.497
H-Index - 78
ISSN - 1482-1826
DOI - 10.18433/j38g7x
Subject(s) - carbamazepine , toxic epidermal necrolysis , oxcarbazepine , lamotrigine , phenytoin , primidone , epilepsy , medicine , phenobarbital , genotyping , pharmacology , dermatology , genotype , genetics , biology , psychiatry , gene
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 HLA-B*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. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.