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Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population

The Pharmacogenomics Journal volume 17, pages 170–173 (2017)Cite this article

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Abstract

Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case–control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.

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Acknowledgements

This study was financially supported by the Ministry of Health, Malaysia and part of the study was funded by the University of Malaya under High Impact Research Grant from the Ministry of Higher Education research fund (reference no.: UM.C/625/1/HIR/MOHE/CHAN-02). We thank all the participating centers for their contributions, and the Director General of Health, Malaysia for permission to publish this paper. We thank Miss Amy Khor Hu Ping for her assistance in genotyping at the University of Malaya.

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Author notes

  1. C-C Chang

    Present address: 8Present address: Gleneagles Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.,

  2. S H Hussein

    Present address: 10Present address: KPJ Damansara Specialist Hospital, Petaling Jaya, Selangor, Malaysia.,

  3. C-C Chang and C-C Ng: These authors contributed equally as first authors.

  4. K-S Lim and S Murad: These authors contributed equally as last authors.

Authors and Affiliations

  1. Department of Dermatology, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia

    C-C Chang & S H Hussein

  2. Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia

    C-C Ng

  3. Allergy and Immunology Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia

    C-L Too & S Murad

  4. Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Malaysia

    S-E Choon

  5. Pantai Hospital Cheras, Kuala Lumpur, Malaysia

    C-K Lee

  6. Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Taipei, Taiwan

    W-H Chung

  7. Division of Neurology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

    K-S Lim

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Correspondence to C-C Chang or C-C Ng.

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Chang, CC., Ng, CC., Too, CL. et al. Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population. Pharmacogenomics J 17, 170–173 (2017). https://doi.org/10.1038/tpj.2016.10

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