Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2016
Coupling 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.
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Teh Lay Kek, Selvaraj Manikandan, Bannur Zakaria, Ismail Mohd Ikhwan Mohd, Rafia Hanip, Law Wan Chung, Sapuan Sapiah, Puvanarajah Santhi, Ali Pakeer Shaik Syed, Salleh Mohd Zaki
Аннотация
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.
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.