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Association of carbamazepine-induced Stevens–Johnson syndrome/toxic epidermal necrolysis with the HLA-B75 serotype or HLA-B*15:21 allele in Filipino patients

The Pharmacogenomics Journal volume 20, pages 533–541 (2020)Cite this article

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Abstract

A case-control study was conducted to investigate the association of HLA-A alleles, HLA-B alleles including HLA-B*15:02 and HLA-B75 serotype with carbamazepine-induced SJS/TEN in Filipino patients. A retrospective review of medical records was performed. Pertinent clinical data were collected. Eight (8) carbamazepine-induced SJS/TEN cases and 32 tolerant controls were recruited. Genomic DNA was extracted from the saliva samples and genotyping was performed by employing allele-specific polymerase chain reaction. Data were analyzed using the Fisher's exact test, Mann–Whitney U test, univariate logistic regression, and multivariate logistic regression. Single allele association analysis was done. The strength of association was expressed as odds ratio with 95% confidence interval. Positive predictive value, negative predictive value, sensitivity, and specificity were computed. Of all the alleles tested, the HLA-B75 serotype (p = 0.007, OR = 23.25, 95% CI = 2.33–232.21) and HLA-B*15:21 (p = 0.026, OR = 7.53, 95% CI = 1.27–44.79) were significantly associated with carbamazepine-induced SJS/TEN. The HLA-B75 serotype or HLA-B*15:21 allele may be used as a genetic risk assessment prior to prescription for prevention of carbamazepine-induced SJS/TEN in Filipino patients.

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Acknowledgements

The authors would like to thank the Department of Medical Sciences, Ministry of Public Health, Thailand for supporting the genotyping done in this study and the Office of Vice President for Academic Affairs, University of the Philippines and the National Institutes of Health, University of the Philippines Manila (grant no.: NIH 2017-001) for its financial support.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand

    Francis Capule & Pramote Tragulpiankit

  2. Department of Pharmacy, College of Pharmacy, University of the Philippines Manila, Manila, Philippines

    Francis Capule

  3. Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand

    Surakameth Mahasirimongkol & Nuanjun Wichukchinda

  4. Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand

    Jiraphun Jittikoon

  5. Section of Allergy and Immunology, Department of Medicine, Philippine General Hospital and College of Medicine, University of the Philippines Manila, Manila, Philippines

    Lara Theresa Alentajan-Aleta & Katrina Faith San Gabriel

  6. Section of Dermatology, Department of Medicine, Philippine General Hospital and College of Medicine, University of the Philippines Manila, Manila, Philippines

    Jay-V James Barit & Francisca Roa

  7. Section of Adult Neurology, Department of Neurosciences, Philippine General Hospital and College of Medicine, University of the Philippines Manila, Manila, Philippines

    Josephine Casanova-Gutierrez, Leonor Cabral-Lim & Jose Paciano Baltazar Reyes

  8. Graduate School, University of the East Ramon Magsaysay Memorial Medical Center, Quezon City, Philippines

    Raymark Salonga

  9. Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Manila, Philippines

    Catherine Lynn Silao

  10. Department of Pediatrics, Philippine General Hospital and College of Medicine, University of the Philippines Manila, Manila, Philippines

    Catherine Lynn Silao

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  1. Francis Capule
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Correspondence to Pramote Tragulpiankit.

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The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the University of the Philippines Manila Research Ethics Board with study protocol code UPMREB 2017-096-01 and by the Faculty of Dentistry and Faculty of Pharmacy Institutional Review Board, Mahidol University with reference number 0517.0319/364.

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Capule, F., Tragulpiankit, P., Mahasirimongkol, S. et al. Association of carbamazepine-induced Stevens–Johnson syndrome/toxic epidermal necrolysis with the HLA-B75 serotype or HLA-B*15:21 allele in Filipino patients. Pharmacogenomics J 20, 533–541 (2020). https://doi.org/10.1038/s41397-019-0143-8

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