HLA-B59:01: a marker for Stevens–Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese

• Published in: The pharmacogenomics journal Vol. 16; no. 1; pp. 83 - 87
• Main Authors: Yang, F, Xuan, J, Chen, J, Zhong, H, Luo, H, Zhou, P, Sun, X, He, L, Chen, S, Cao, Z, Luo, X, Xing, Q
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2016; Nature Publishing Group
• Subjects: 45/23; 692/53/2421; Adult; Aged; Asian Continental Ancestry Group; Biomedical and Life Sciences; Biomedicine; Carbonic Anhydrase Inhibitors - adverse effects; Case-Control Studies; Complications and side effects; Female; Gene Expression; Genetic aspects; Genetic Association Studies; Genetic Markers; Genetic research; Genetic susceptibility; Genotype; Genotypes; Glaucoma; Haplotypes; Histocompatibility antigen HLA; HLA-B Antigens - genetics; Human Genetics; Humans; Major histocompatibility complex; Male; Methazolamide; Methazolamide - adverse effects; Middle Aged; Molecular Docking Simulation; Molecular Dynamics Simulation; Oncology; original-article; Patients; Pharmacotherapy; Psychopharmacology; Risk factors; Skin diseases; Stevens-Johnson syndrome; Stevens-Johnson Syndrome - drug therapy; Stevens-Johnson Syndrome - ethnology; Stevens-Johnson Syndrome - genetics; Toxic epidermal necrolysis
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2015.25

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.