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Association of HLA polymorphisms and acetaminophen-related Steven-Johnson syndrome with severe ocular complications in Thai population
  1. Passara Jongkhajornpong1,
  2. Mayumi Ueta2,
  3. Kaevalin Lekhanont1,
  4. Vilavun Puangsricharern3,
  5. Pinnita Prabhasawat4,
  6. Patchima Chantaren3,
  7. Phattrawan Pisuchpen3,
  8. Shigeru Kinoshita5
  1. 1Ophthalmology, Ramathibodi Hospital, Bangkok, Thailand
  2. 2Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  3. 3Ophthalmology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand
  4. 4Ophthalmology, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
  5. 5Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
  1. Correspondence to Dr Mayumi Ueta, Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan; mueta{at}


Background/aims To investigate the association of genetic polymorphisms of human leucocyte antigens (HLA) class I and II genes with acetaminophen-related Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) who developed severe ocular complications (SOC) in the Thai population.

Methods A prospective case–control study including 20 unrelated Thai acetaminophen-related SJS/TEN patients with SOC and 60 Thai healthy volunteers, recruited at three university hospitals in Bangkok, Thailand, from September 2014 to August 2019. HLA genes were analysed using PCR amplification followed by hybridisation with sequence-specific oligonucleotide (SSO) probes with bead-based typing kits. The carrier and gene frequencies of individual HLA alleles in patients were compared with those in control volunteers based on dominant assumption using Fisher’s exact test.

Results Among HLA class I polymorphisms, HLA-A*33:03, HLA-B*44:03 and HLA-C*07:01 were significantly associated with acetaminophen-related SJS/TEN and SOC with high ORs (95% CI, corrected p value; Pc) in carrier frequency of 5.4 (1.8 to 16.3, Pc=0.0274), 9.0 (95% CI 2.7 to 30.4, Pc=0.0034), and 9.3 (2.8 to 30.2, Pc=0.0022), respectively. There were no significant HLA class II associations with the disease after corrected for a total number of alleles tested.

Conclusion HLA-B*44:03 was strongly associated with acetaminophen-related SJS/TEN patients who developed SOC in Thai population. In addition, we also found moderate to strong associations with HLA-A*33:03 and HLA-C*07:01 suggesting their potential roles in the pathogenesis of SOC in acetaminophen-related SJS/TEN.

  • genetics
  • ocular surface

Statistics from


  • PJ and MU contributed equally.

  • Contributors MU planned the research design. PJ, KL, PiP, PC, VP and PhP collected samples. SK, MU and PJ analysed the data. PJ and MU prepared the manuscript draft with important intellectual from PPi, VP and SK. All authors approved the final manuscript.

  • Funding This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government (no. 19H03809), and by the JSPS Core-to-Core Program, A. Advanced Research Networks.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study protocols were approved by the Institutional Review Board of all institutes. All experimental procedures complied with the principles set forth in the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. The data in this research are available on reasonable request to the corresponding author.

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