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
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DOI：
10.1038/tpj.2015.25
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发表时间：
2016-02-01
影响因子：
2.8
通讯作者：
Xing, Q.
中科院分区：
文献类型：
--
作者：
Yang, F.;Xuan, J.;Xing, Q.
醋甲唑胺是一种降低眼内压的药物，用于治疗青光眼和其他眼科异常。醋甲唑胺的使用已被证明可导致亚洲血统患者的Stevens-Johnson综合征（SJS）和中毒性表皮坏死松解症（TEN）。醋甲唑胺诱导的SJS/TEN与韩国和日本人群中HLA-B59血清型/HLAB* 59：01的存在相关。为了更好地了解中国汉族人群中这些不良反应的遗传风险因素，我们描述了2008年至2014年8例醋甲唑胺诱导的SJS/TEN中国患者的HLA I类基因型。病例组HLA-B* 59：01的频率为87.5%（7/8），而耐甲唑胺组为0%（0/30），差异有显著性（OR = 305.0; P = 6.3 x 10（-7））和0.35%（1/283）的健康受试者（OR = 1974.0; P = 2.0 x 10（-12））。HLA-C* 01：02与HLA-B* 59：01密切相关，与耐受对照组（OR = 12.1; P = 0.016）和一般人群（OR = 15.5; P = 2.0 x 10（-3））相比，与醋唑胺诱导的SJS/TEN有较弱但显著的相关性。HLA-B* 59：01-C* 01：02单倍型的分布在病例组和对照组中也有显著差异。本研究首次证实了HLA-B* 59：01与醋甲唑胺诱导的中国汉族人群SJS/TEN之间的强相关性。治疗前筛查HLA-B* 59：01将有助于降低醋甲唑胺诱导的SJS/TEN的风险。
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/HLAB* 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 x 10(-7)) and 0.35% (1/283) in healthy subjects from the human major histocompatibility complex database (OR = 1974.0; P = 2.0 x 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 x 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.