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Association of human antigen class I genes with cold medicine-related Stevens-Johnson syndrome with severe ocular complications in a Korean population
  1. Ikhyun Jun1,2,
  2. John Hoon Rim2,3,
  3. Mee Kum Kim4,
  4. Kyung-Chul Yoon5,
  5. Choun-Ki Joo6,
  6. Shigeru Kinoshita7,
  7. Kyoung Yul Seo1,
  8. Mayumi Ueta7
  1. 1 Department of Ophthalmology, The Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea
  2. 2 Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea
  3. 3 Department of Medicine, Physician-Scientist Program, Yonsei University Graduate School of Medicine, Seoul, Korea
  4. 4 Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea
  5. 5 Department of Ophthalmology, Chonnam National University, Gwangju, Korea
  6. 6 Department of Ophthalmology and Visual Science, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
  7. 7 Department of Frontier Medical Science and Technology for Ophthalmology, 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, Japan; mueta{at}koto.kpu-m.ac.jp; Dr Kyoung Yul Seo, Department of Ophthalmology, Yonsei University College of Medicine, Seoul 03722, Korea; seoky{at}yuhs.ac

Abstract

Background/aims Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a spectrum of diseases that cause an acute vesiculobullous reaction in the skin and mucous membranes. The occurrence of these diseases is associated with various drugs, a large proportion of which is comprised cold medicines (CM). We try to investigate the association between human leucocyte antigen (HLA) class I genes and CM-related SJS/TEN (CM-SJS/TEN) with severe ocular complications (SOC) in the Korean population.

Methods This multicentre case-control study enrolled 40 Korean patients with CM-SJS/TEN with SOC and 120 age-matched and sex-matched Korean healthy volunteers between January 2012 and May 2014. HLA genotyping was performed using PCR followed by hybridisation with sequence-specific oligonucleotide probes.

Results The carrier frequency and gene frequency of HLA-A*02:06 were 37.5 % and 20.0 %, respectively, in patients, and 16.7 % and 9.6 %, respectively, in controls (p=0.018). The carrier frequency of HLA-C*03:04 was 30 % in patients and 10.8 % in controls, and gene frequency of HLA-C*03:04 was 15 % in patients and 5.4 % in controls (p=0.003). The carrier frequency and gene frequency of HLA-C*03:03 were 2.5 % and 1.3 %, respectively, in patients, and 20 % and 10.4 %, respectively, in controls (p=0.006).

Conclusions As per our results, we suggest that HLA-A*02:06 and HLA-C*03:04 might be positive markers for CM-SJS/TEN with SOC, and HLA-C*03:03 might be an indicator of protection against CM-SJS/TEN with SOC in the Korean population.

  • experimental &#8211 laboratory
  • genetics
  • ocular surface

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Footnotes

  • Contributors MKK, KCY, CKJ, SK, KYS, MU: conceived and designed the study. SK, MU: conducted the experiments. IJ, JHR: analysed the results. IJ, KYS, MU: wrote the main manuscript. MKK, KCY, CKJ, SK: did critical revision of the manuscript for important intellectual content. All authors contributed to the review of the literature, in drafting the manuscript and in approving the final manuscript.

  • Funding This work was supported partly by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government and the JSPS Core-to-Core Program, A. Advanced Research Networks (MU) and grants NRF-2013M3A9D5072551 (KYS) from the Bio & Medical Technology Development Program of the National Research Foundation funded by the Ministry of Science, ICT and Future Planning.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval The study was approved by the institutional review board of of the Yonsei University College of Medicine, Seoul National University College of Medicine, Chonnam National University Medical School and College of Medicine, Catholic University of Korea and Kyoto Prefectural University of Medicine.

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

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