{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:12:18Z","timestamp":1780636338899,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Methazolamide (MTZ) has been occasionally linked to the lethal Stevens\u2013Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are associated with <jats:italic>HLA\u2010B*59:01<\/jats:italic>. However, some MTZ\u2010induced SJS\/TEN (MTZ\u2010SJS\/TEN) cases are negative for <jats:italic>HLA\u2010B*59:01<\/jats:italic>, implying that other genetic factors besides <jats:italic>HLA\u2010B*59:01<\/jats:italic> are contributing to MTZ\u2010SJS\/TEN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To comprehensively identify <jats:italic>HLA<\/jats:italic> and non\u2010<jats:italic>HLA<\/jats:italic> genetic susceptibility to MTZ\u2010SJS\/TEN in Han Chinese.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighteen patients with MTZ\u2010SJS\/TEN, 806 subjects of the population control and 74 MTZ\u2010tolerant individuals were enrolled in this study. Both exome\u2010wide and HLA\u2010based association studies were conducted. Molecular docking analysis was employed to simulate the interactions between MTZ and risk HLA proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found a strong signal in the major histocompatibility complex region on chromosome 6 with 22 SNPs reaching exome\u2010wide significance. Compared with MTZ\u2010tolerant controls, a significant association of <jats:italic>HLA\u2010B*59:01<\/jats:italic> with MTZ\u2010SJS\/TEN was validated [odds ratio (OR)\u2009=\u2009146.00, 95% confidence interval (CI): 16.12\u20131321.98; <jats:italic>P<\/jats:italic>\u2009=\u20096.19\u2009\u00d7\u200910<jats:sup>\u221210<\/jats:sup>]. Moreover, 66.7% of MTZ\u2010SJS\/TEN patients negative for <jats:italic>HLA\u2010B*59:01<\/jats:italic> were carriers of <jats:italic>HLA\u2010B*55:02<\/jats:italic>, whilst 2.7% of the tolerant individuals were observed with <jats:italic>HLA\u2010B*55:02<\/jats:italic> (OR\u2009=\u200971.00, 95% CI: 7.84\u2013643.10; <jats:italic>P<\/jats:italic>\u2009=\u20091.43\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>). Within HLA\u2010B protein, the E45\u2010L116 motif could completely explain the association of <jats:italic>HLA\u2010B*59:01<\/jats:italic> and <jats:italic>HLA\u2010B*55:02<\/jats:italic> with MTZ\u2010SJS\/TEN (OR\u2009=\u2009119.33, 95% CI: 29.19\u20131227.96; <jats:italic>P<\/jats:italic>\u2009=\u20094.36\u2009\u00d7\u200910<jats:sup>\u221213<\/jats:sup>). Molecular docking analysis indicated that MTZ binds more stably to the pocket of HLA\u2010B*59:01 and HLA\u2010B*55:02 than to that of non\u2010risk alleles of HLA\u2010B*40:01 and HLA\u2010C*01:02.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study confirmed the association of <jats:italic>HLA<\/jats:italic>\u2010<jats:italic>B*59:01<\/jats:italic> with MTZ\u2010SJS\/TEN and identified <jats:italic>HLA\u2010B*55:02<\/jats:italic> as a novel risk allele in Han Chinese with the largest sample size to date. Notably, the rs41562914(A)\u2010rs12697944(A) haplotype, encoding E45\u2010L116, is capable of serving as a powerful genetic predictor for MTZ\u2010SJS\/TEN with a sensitivity of 89% and specificity of 96%.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.17980","type":"journal-article","created":{"date-parts":[[2022,2,5]],"date-time":"2022-02-05T17:33:43Z","timestamp":1644082423000},"page":"873-880","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Unique motif shared by HLA\u2010B*59:01 and HLA\u2010B*55:02 is associated with methazolamide\u2010induced Stevens\u2013Johnson syndrome and toxic epidermal necrolysis in Han Chinese"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4228-7735","authenticated-orcid":false,"given":"M.","family":"Jiang","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital &amp; Institutes of Biomedical Sciences Fudan University  Shanghai 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