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

Authors

  • Lay Kek Teh Integrative Pharmacogenomics Institute, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia. Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia.
  • Manikandan Selvaraj Integrative Pharmacogenomics Institute, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia.
  • Zakaria Bannur Integrative Pharmacogenomics Institute, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia.
  • Mohd Ikhwan Mohd Ismail Integrative Pharmacogenomics Institute, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia.
  • Hanip Rafia Neurology Institute, Hospital Kuala Lumpur, Malaysia.
  • Wan Chung Law Neurology Institute, Hospital Kuala Lumpur, Malaysia.
  • Sapiah Sapuan Neurology Institute, Hospital Kuala Lumpur, Malaysia.
  • Santhi Puvanarajah Neurology Institute, Hospital Kuala Lumpur, Malaysia.
  • Pakeer Shaik Syed Ali Integrative Pharmacogenomics Institute, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia.
  • Mohd Zaki Salleh Integrative Pharmacogenomics Institute, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia. Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia.

DOI:

https://doi.org/10.18433/J38G7X

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 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.

 

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Published

2016-03-24

How to Cite

Teh, L. K., Selvaraj, M., Bannur, Z., Ismail, M. I. M., Rafia, H., Law, W. C., … Salleh, M. Z. (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. Journal of Pharmacy & Pharmaceutical Sciences, 19(1), 147–160. https://doi.org/10.18433/J38G7X

Issue

Section

Clinical Pharmacology and Therapeutics