Yang F, Xuan J, Chen J, Zhong H, Luo H, Zhou P, Sun X, He L, Chen S, Cao Z, Luo X, Xing Q
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Pharmacogenomics J. 2016 Feb;16(1):83-7. doi: 10.1038/tpj.2015.25. Epub 2015 Apr 28.
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-B59:01 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-B59:01 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-C01:02, which is closely linked to HLA-B59:01, 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-B59:01-C01:02 haplotype was also significantly different in cases and controls. This study demonstrated a strong association between HLA-B59:01 and methazolamide-induced SJS/TEN in the Han Chinese population for the first time. Pretherapy screening for HLA-B59:01 would be useful to reduce the risk of methazolamide-induced SJS/TEN.
醋甲唑胺是一种降低眼压的药物，用于治疗青光眼和其他眼科异常。已表明使用醋甲唑胺会在亚洲血统患者中引起史蒂文斯 - 约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）。在韩国和日本人群中，醋甲唑胺诱导的SJS/TEN与HLA - B59血清型/HLA - B59:01的存在有关。为了更好地了解汉族人群中这些不良反应的遗传风险因素，我们对2008年至2014年8例因醋甲唑胺诱导SJS/TEN的中国患者的HLA I类基因型进行了特征分析。病例患者中HLA - B59:01的频率为87.5%（7/8），这与耐受醋甲唑胺的患者中的0%（0/30）（优势比（OR）=305.0；P = 6.3×10⁻⁷）以及人类主要组织相容性复合体数据库中健康受试者的0.35%（1/283）（OR = 1974.0；P = 2.0×10⁻¹²）有显著差异。与HLA - B59:01紧密连锁的HLA - C01:02与醋甲唑胺诱导的SJS/TEN相比，与耐受对照组（OR = 12.1；P = 0.016）和普通人群（OR = 15.5；P = 2.0×10⁻³）有较弱但显著的关联。HLA - B59:01 - C01:02单倍型在病例组和对照组中的分布也有显著差异。本研究首次证明了汉族人群中HLA - B59:01与醋甲唑胺诱导的SJS/TEN之间存在强关联。治疗前筛查HLA - B59:01有助于降低醋甲唑胺诱导SJS/TEN的风险。
