TY - JOUR
T1 - 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
AU - Teh, Lay Kek
AU - Selvaraj, Manikandan
AU - Bannur, Zakaria
AU - Ismail, Mohd Ikhwan Mohd
AU - Rafia, Md Hanip
AU - Law, Wan Chung
AU - Sapuan, Sapiah
AU - Puvanarajah, Santhi
AU - Ali, Pakeer Shaik Syed
AU - Salleh, Mohd Zaki
N1 - Publisher Copyright:
© 2016, Canadian Society for Pharmaceutical Sciences. All rights reserved.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/3/24
Y1 - 2016/3/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84961762798&partnerID=8YFLogxK
U2 - 10.18433/J38G7X
DO - 10.18433/J38G7X
M3 - Article
C2 - 27096699
AN - SCOPUS:84961762798
SN - 1482-1826
VL - 19
SP - 147
EP - 160
JO - Journal of Pharmacy and Pharmaceutical Sciences
JF - Journal of Pharmacy and Pharmaceutical Sciences
IS - 1
ER -