日本人におけるスルホンアミド系薬剤による重症薬疹の発症と<i>HLA-A*11:01</i>の関連
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- Ryosuke NAKAMURA
- Division of Medicinal Safety Science, National Institute of Health Sciences
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- Takeshi OZEKI
- Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences
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- Noriaki HIRAYAMA
- Institute of Advanced Biosciences, Tokai University
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- Akihiro SEKINE
- Center for Preventive Medical Science, Chiba University
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- Yoshiko MIZUKAWA
- Department of Dermatology, Kyorin University School of Medicine
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- Tetsuo SHIOHARA
- Department of Dermatology, Kyorin University School of Medicine
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- Hideaki WATANABE
- Dermatology, Showa University School of Medicine
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- Hirohiko SUEKI
- Dermatology, Showa University School of Medicine
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- Kohei OGAWA
- Department of Dermatology, Nara Medical University
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- Hideo ASADA
- Department of Dermatology, Nara Medical University
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- Eri TSUKAGOSHI
- Division of Medicinal Safety Science, National Institute of Health Sciences
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- Kayoko MATSUNAGA
- Department of Integrative Medical Science for Allergic Disease, Fujita Health University School of Medicine
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- Hiroyuki NIIHARA
- Department of Dermatology, Shimane University Faculty of Medicine
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- Yukie YAMAGUCHI
- Department of Environmental Immuno- Dermatology, Yokohama City University Graduate School of Medicine
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- Michiko AIHARA
- Department of Environmental Immuno- Dermatology, Yokohama City University Graduate School of Medicine
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- Taisei MUSHIRODA
- Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences
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- Yoshiro SAITO
- Division of Medicinal Safety Science, National Institute of Health Sciences
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- Eishin MORITA
- Department of Dermatology, Shimane University Faculty of Medicine
書誌事項
- タイトル別名
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- Association of <i>HLA-A*11:01</i> with sulfonamide-related severe cutaneous adverse reactions in Japanese
抄録
<p>[Aim] Sulfonamides can cause Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug-induced hypersensitivity syndrome (DIHS) as known as severe cutaneous adverse reactions (SCARs). Sulfamethoxazole (SMX) and salazosulfapyridine (SASP) are the most common sulfonamides used in Japan. We sought for new risk HLA candidates associated with the onset of sulfonamide-related SCARs in the Japanese patients.</p><p></p><p>[Materials and Methods] In total, 8 SJS/TEN and 7 DIHS patients were recruited under written informed consent through the nationwide case-collecting network system and the institutes belonging to the Japanese Research Committee on Severe Cutaneous Adverse Reaction, respectively. Each patient had taken SMX or SASP. HLA types and genome-wide single nucleotide polymorphisms (SNPs) were determined by Luminex and illumina BeadChip, respectively. The docking simulations were performed by using ASEDock software.</p><p></p><p>[Results and Discussion] We independently examined HLA types associated with SJS/TEN and DIHS cases in Japan and found a significantly higher prevalence of HLA-A*11:01 in both cases than in healthy volunteer population (odds ratio = 9.84; P = 2.67×10−5). Furthermore, we performed in silico docking simulations to predict interactions between HLA and sulfonamides SMX and SASP and found that they bound the peptide-binding groove of HLA-A*11:01 with binding energies of −5.60 and −6.67 kcal/mol, respectively. These findings suggested HLA-A*11:01 as a risk factor for sulfonamide-related onset of SCARs in the Japanese population.</p>
収録刊行物
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- 日本毒性学会学術年会
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日本毒性学会学術年会 49.1 (0), P-195-, 2022
日本毒性学会