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.
OBJECTIVE
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.
Integrative Pharmacogenomics Institute, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia. Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia.
Lay Kek
LK
Teh
Manikandan
M
Selvaraj
Zakaria
Z
Bannur
Mohd Ikhwan Mohd
MI
Ismail
Hanip
H
Rafia
Wan Chung
WC
Law
Sapiah
S
Sapuan
Santhi
S
Puvanarajah
Pakeer Shaik Syed
PS
Ali
Mohd Zaki
MZ
Salleh
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000737:chemistry; D002220:Carbamazepine / Q000009:adverse effects* / Q000737:chemistry; D005260:Female; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D062105:Molecular Docking Simulation; D013262:Stevens-Johnson Syndrome / Q000188:drug therapy* / Q000235:genetics*; D055815:Young Adult
D000927:Anticonvulsants; D015235:HLA-B Antigens; D002220:Carbamazepine