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

Expert Opin Drug Saf. 2020 Oct;19(10):1349-1356. doi: 10.1080/14740338.2020.1796965. Epub 2020 Aug 18.

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; HLA-B*13:01; human leukocyte antigen; hypersensitivity syndrome.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics
  • Child
  • Dapsone / administration & dosage
  • Dapsone / adverse effects*
  • Drug Hypersensitivity Syndrome / etiology*
  • Drug Hypersensitivity Syndrome / genetics
  • Female
  • Genotype
  • HLA-B13 Antigen / genetics*
  • Humans
  • Leprostatic Agents / administration & dosage
  • Leprostatic Agents / adverse effects*
  • Male
  • Middle Aged
  • Registries
  • Republic of Korea
  • Risk Factors

Substances

  • HLA-B13 Antigen
  • Leprostatic Agents
  • Dapsone