HLA-B*59:01: a marker for Stevens-Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese.
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.
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
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F
Yang
Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
J
J
Xuan
Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, China.
J
J
Chen
Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
H
H
Zhong
University of Arkansas at Little Rock/University of Arkansas for Medical Sciences Joint Bioinformatics Program, Little Rock, AR, USA.
H
H
Luo
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
P
Zhou
Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, China.
X
X
Sun
Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
L
L
He
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
S
S
Chen
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
Z
Z
Cao
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.
X
X
Luo
Children's Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Q
Q
Xing
D000328:Adult; D000368:Aged; D044466:Asian People; D002257:Carbonic Anhydrase Inhibitors / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008704:Methazolamide / Q000009:adverse effects*; D008875:Middle Aged; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D013262:Stevens-Johnson Syndrome / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics
D002257:Carbonic Anhydrase Inhibitors; D005819:Genetic Markers; D015235:HLA-B Antigens; C082943:HLA-B59 antigen; D008704:Methazolamide