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

The Pharmacogenomics Journal volume 16, pages 83–87 (2016)Cite this article

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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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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grants 81472873, 81071287, 30971582 and 31371274) and the Shanghai Municipal Commission of Science and Technology Program (14DJ1400100).

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Author notes

  1. J Xuan

    Present address: 7Current address: National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.,

  2. F Yang, J Xuan and J Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China

    F Yang, S Chen, Z Cao & X Luo

  2. Children’s Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China

    J Xuan, H Zhong, L He & Q Xing

  3. Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, China

    J Chen & X Sun

  4. University of Arkansas at Little Rock/University of Arkansas for Medical Sciences Joint Bioinformatics Program, Little Rock, AR, USA

    H Luo

  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

    P Zhou

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Correspondence to X Luo or Q Xing.

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Yang, F., Xuan, J., Chen, J. et al. HLA-B*59:01: a marker for Stevens–Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese. Pharmacogenomics J 16, 83–87 (2016). https://doi.org/10.1038/tpj.2015.25

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