The HLA-B*13:01 and the dapsone hypersensitivity syndrome in Korean and Asian populations: genotype- and meta-analyses

ABSTRACT

Background

The human leukocyte antigen (HLA)-B*13:01 was reported as an important risk factor for dapsone hypersensitivity syndrome (DHS) in Chinese and Thai populations.

Research design and methods

From the Korean nationwide registry, seven subjects with previous DHS were included. Their HLA allele/phenotype frequencies were compared with 8 dapsone-tolerant subjects recruited from a single institution, and general population (n = 485) in Korea. The authors also performed a meta-analysis with these data using previous Chinese and Thai studies.

Results

Among the seven DHS subjects, 85.7% presented with the HLA-B*13:01 allele. The HLA-C*03:04, HLA-DRB1*12:02 (both in linkage disequilibrium with HLA-B*13:01), and HLA-A*02:01 alleles were also presented in 85.7%, 71.4%, and 71.4%, respectively. Subjects with HLA-B*13:01 were susceptible to developing DHS compared to dapsone-tolerant controls (odds ratio [OR]: 73.667) and the Korean general population (OR: 139.500). HLA-C*03:04 (OR: 40.935), HLA-DRB*12:02 (OR: 36.613), and HLA-A*02:01 (OR: 5.862) showed similar results. In meta-analysis, HLA-B*13:01 was associated with dapsone-induced hypersensitivity (overall OR: 42.692), and subgroup analyses according to the control types demonstrated similar results (OR:43.694 and 41.866, respectively).

Conclusions

Similar to previous Asian population studies, HLA-B*13:01 is significantly associated with the risk of DHS in Korea. These associations may be useful for preventing DHS and improving drug safety.

KEYWORDS:

• Dapsone
• human leukocyte antigen
• HLA-B*13:01
• hypersensitivity syndrome

Author contributions

Hye Jung Park: She made a significant contribution to the work in the study design, execution, acquisition of data, analysis, and interpretation. She wrote the draft and revised the article. She agreed on the journal to which the article will be submitted. She reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage. She agreed to take responsibility and be accountable for the contents of the article and to share responsibility to resolve any questions raised about the accuracy or integrity of the published work. Jung-Won Park, Sae Hoon Kim, So-Yun Choi, Hee-Kyoo Kim, Chang-Gyu Jung, Min-Suk Yang, Dong Yoon Kang, Min-Kyoung Cho, and Hyouk-Soo Kwon: They made a significant contribution to the work in acquisition of data, analysis and interpretation. They critically reviewed the article. They agreed on the journal to which the article will be submitted. They reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage. They agreed to take responsibility and be accountable for the contents of the article and to share responsibility to resolve any questions raised about the accuracy or integrity of the published work. Hye-Ryun Kang: She suggested critical concept of this study. She also a significant contribution to the work in the study design, execution, acquisition of data, analysis and interpretation. She critically reviewed the article. She agreed on the journal to which the article will be submitted. She reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage. She agreed to take responsibility and be accountable for the contents of the article and to share responsibility to resolve any questions raised about the accuracy or integrity of the published work. Yong Won Lee: He provided constructive criticism on the rationale and design of this study. He also significant contribution to the work in the study design, execution, acquisition of data, analysis, and interpretation. He critically reviewed the article. He agreed on the journal to which the article will be submitted. He reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and any significant changes introduced at the proofing stage. He agreed to take responsibility and be accountable for the contents of the article and to share responsibility to resolve any questions raised about the accuracy or integrity of the published work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research was supported by a grant to operation of the regional pharmacovigilance center in 2019 and a grant [18182MFDS411] in 2018 from the Ministry of Food and Drug Safety.