2. Academic Validation
  3. HLA-B*59:01: a marker for Stevens-Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese

HLA-B*59:01: a marker for Stevens-Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese

  • Pharmacogenomics J. 2016 Feb;16(1):83-7. doi: 10.1038/tpj.2015.25.
F Yang 1,  J Xuan 2,  J Chen 3,  H Zhong 2,  H Luo 4,  P Zhou 5,  X Sun 3,  L He 2,  S Chen 1,  Z Cao 1,  X Luo 1,  Q Xing 2
Affiliations

Affiliations

  • 1 Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
  • 2 Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • 3 Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, China.
  • 4 University of Arkansas at Little Rock/University of Arkansas for Medical Sciences Joint Bioinformatics Program, Little Rock, AR, USA.
  • 5 Center of Bioinformatics (COBI) and Key Laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
PMID: 25918017 DOI: 10.1038/tpj.2015.25
Abstract

Methazolamide is an intraocular pressure-lowering drug that is used in the treatment of glaucoma and other ophthalmologic abnormalities. The use of methazolamide has been shown to cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients of Asian ancestry. Methazolamide-induced SJS/TEN is associated with the presence of HLA-B59 serotype/HLA-B*59:01 in Korean and Japanese populations. To better understand the genetic risk factors for these adverse reactions in the Han Chinese population, we characterized the HLA class I genotypes of eight Chinese patients with methazolamide-induced SJS/TEN from 2008 to 2014. The frequency of HLA-B*59:01 was 87.5% (7/8) in the case patients, which was significantly different from 0% (0/30) in the methazolamide-tolerant patients (odds ratio (OR)=305.0; P=6.3 × 10(-7)) and 0.35% (1/283) in healthy subjects from the human major histocompatibility complex database (OR=1974.0; P=2.0 × 10(-12)). HLA-C*01:02, which is closely linked to HLA-B*59:01, had a weaker but notable association with methazolamide-induced SJS/TEN compared with the tolerant controls (OR=12.1; P=0.016) and general population (OR=15.5; P=2.0 × 10(-3)). The distribution of the HLA-B*59:01-C*01:02 haplotype was also significantly different in cases and controls. This study demonstrated a strong association between HLA-B*59:01 and methazolamide-induced SJS/TEN in the Han Chinese population for the first time. Pretherapy screening for HLA-B*59:01 would be useful to reduce the risk of methazolamide-induced SJS/TEN.

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