Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease
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- Kaoru Suzuki
- Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai, Japan
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- Yoichi Kakuta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai, Japan
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- Takeo Naito
- Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai, Japan
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- Tetsuya Takagawa
- Center for Inflammatory Bowel Disease, Division of Internal Medicine, Hyogo College of Medicine , Nishinomiya, Japan
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- Hiroyuki Hanai
- Hamamatsu Rosai Hospital , Hamamatsu, Japan
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- Hiroshi Araki
- Department of Gastroenterology, Gifu University Graduate School of Medicine , Gifu, Japan
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- Yu Sasaki
- Department of Gastroenterology, Yamagata University Faculty of Medicine , Yamagata, Japan
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- Hirotake Sakuraba
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine , Hirosaki, Japan
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- Makoto Sasaki
- Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine , Nagakute, Japan
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- Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine , Mitaka, Japan
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- Satoshi Motoya
- IBD Center, Sapporo-Kosei General Hospital , Sapporo, Japan
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- Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, Iwate Medical University , Morioka, Japan
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- Motoyuki Onodera
- Department of Gastroenterology, Iwate Prefectural Isawa Hospital , Iwate, Japan
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- Yoh Ishiguro
- Department of Gastroenterology and Hematology, Hirosaki National Hospital , Hirosaki, Japan
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- Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine , Sapporo, Japan
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- Akira Andoh
- Department of Gastroenterology, Shiga University of Medical Science , Otsu, Japan
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- Sakiko Hiraoka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences , Okayama, Japan
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- Masaru Shinozaki
- Department of Surgery, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan
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- Toshimitsu Fujii
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University , Tokyo, Japan
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- Takehiko Katsurada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo , Japan
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- Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital , Tokyo, Japan
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- Mikihiro Fujiya
- Department of Medicine, Division of Gastroenterology and Hematology/Oncology, Asahikawa Medical University , Asahikawa, Japan
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- Takafumi Otsuka
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Hyogo, Japan
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- Naoki Oshima
- Department of Internal Medicine II, Shimane University Faculty of Medicine , Shimane, Japan
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- Yasuo Suzuki
- Department of Internal Medicine, Toho University Sakura Medical Center , Sakura, Japan
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- Yuichirou Sato
- Department of Gastroenterology, Osaki Citizen Hospital , Osaki, Japan
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- Ryota Hokari
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Defense Medical College , Tokorozawa, Japan
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- Mitsunori Noguchi
- Noguchi Clinic , Sendai, Japan
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- Yuki Ohta
- Department of Gastroenterology, Graduate School of Medicine, Chiba University , Chiba, Japan
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- Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine , Mitaka, Japan
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- Yosuke Kawai
- Genome Medical Science Project, National Center for Global Health and Medicine , Tokyo, Japan
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- Katsushi Tokunaga
- Genome Medical Science Project, National Center for Global Health and Medicine , Tokyo, Japan
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- Masao Nagasaki
- Human Biosciences Unit for the Top Global Course Center for the Promotion of Interdisciplinary Education and Research, Kyoto University , Kyoto, Japan
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- Hisaaki Kudo
- Department of Biobank, Tohoku Medical Megabank Organization, Tohoku University , Sendai, Japan
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- Naoko Minegishi
- Department of Biobank, Tohoku Medical Megabank Organization, Tohoku University , Sendai, Japan
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- Daisuke Okamoto
- Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai, Japan
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- Yusuke Shimoyama
- Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai, Japan
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- Rintaro Moroi
- Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai, Japan
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- Masatake Kuroha
- Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai, Japan
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- Hisashi Shiga
- Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai, Japan
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- Dalin Li
- F. Widjaja Foundation Inflammatory Bowel and Immunology Research Institute, Cedars-Sinai Medical Center , Los Angeles, CA, USA
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- Dermot P B McGovern
- F. Widjaja Foundation Inflammatory Bowel and Immunology Research Institute, Cedars-Sinai Medical Center , Los Angeles, CA, USA
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- Yoshitaka Kinouchi
- Health Administration Center, Center for the Advancement of Higher Education, Tohoku University , Sendai, Japan
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- Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai, Japan
抄録
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called “mesalamine allergy,” which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn’s disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Mesalamine allergy was more common in ulcerative colitis than in Crohn’s disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event.</jats:p> </jats:sec>
収録刊行物
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- Inflammatory Bowel Diseases
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Inflammatory Bowel Diseases 28 (1), 21-31, 2021-01-27
Oxford University Press (OUP)
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詳細情報 詳細情報について
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- CRID
- 1360290617648815232
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- ISSN
- 15364844
- 10780998
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- データソース種別
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- Crossref
- KAKEN