Reducing severe cutaneous adverse and type B adverse drug reactions using pre-stored human leukocyte antigen genotypes

Kye Hwa Lee, Dong Yoon Kang, Hyun Hwa Kim, Yi Jun Kim, Hyo Jung Kim, Ju Han Kim, Eun Young Song, James Yun, Hye Ryun Kang

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3 Scopus citations


Background: Several type B adverse drug reactions (ADRs), especially severe cutaneous adverse reactions (SCARs), are associated with particular human leukocyte antigen (HLA) genotypes. However, pre-stored HLA information obtained from other clinical workups has not been used to prevent ADRs. We aimed to simulate the preemptive use of pre-stored HLA information in electronic medical records to evaluate whether this information can prevent ADRs. Methods: We analyzed the incidence and the risk of ADRs for selected HLA alleles (HLA-B*57:01, HLA-B*58:01, HLA-A*31:01, HLA-B*15:02, HLA-B*15:11, HLA-B*13:01, HLA-B*59:01, and HLA-A*32:01) and seven drugs (abacavir, allopurinol, carbamazepine, oxcarbazepine, dapsone, methazolamide, and vancomycin) using pre-stored HLA information of transplant patients based on the Pharmacogenomics Knowledge Base guidelines and experts' consensus. Results: Among 11,988 HLA-tested transplant patients, 4092 (34.1%) had high-risk HLA alleles, 4583 (38.2%) were prescribed risk drugs, and 580 (4.8%) experienced type B ADRs. Patients with HLA-B*58:01 had a significantly higher incidence of type B ADR and SCARs associated with allopurinol use than that of patients without HLA-B*58:01 (17.2% vs. 11.9%, odds ratio [OR] 1.53 [95% confidence interval {CI} 1.09–2.13], p = 0.001, 2.3% versus 0.3%, OR 7.13 [95% CI 2.19–22.69], p < 0.001). Higher risks of type B ADR and SCARs were observed in patients taking carbamazepine or oxcarbazepine if they had one of HLA-A*31:01, HLA-B*15:02, or HLA-B*15:11 alleles. Vancomycin and dapsone use in HLA-A*32:01 and HLA-B*13:01 carriers, respectively, showed trends toward increased risk of type B ADRs. Conclusion: Utilization of pre-stored HLA data can prevent type B ADRs including SCARs by screening high-risk patients.

Original languageEnglish
Article numbere12098
JournalClinical and Translational Allergy
Issue number1
StatePublished - Jan 2022

Bibliographical note

Funding Information:
This research was supported by a grant (20182MFDS445) from the Ministry of Food and Drug Safety and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HR21C0198).

Publisher Copyright:
© 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.


  • humanes leukozytenantigen
  • pharmakogenomik
  • präventive genotypisierung
  • uberempfindlichkeit
  • unerwünschte arzneimittelwirkung


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