Personal genomics analysis in the inflammatory bowel disease family

• Project/Area Number: 16K09317
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: Naishiro Yasuyoshi 札幌医科大学, 医学部, 研究員 (80347161)
• Co-Investigator(Kenkyū-buntansha): 有村 佳昭 札幌医科大学, 医学部, 研究員 (80305218) ; 仲瀬 裕志 札幌医科大学, 医学部, 教授 (60362498)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 疾患感受性遺伝子 / 炎症性腸疾患 / 日本人 / パーソナルゲノミクス解析 / 希少変異 / 低頻度多型 / パーソナ ルゲノミクス解析

Outline of Final Research Achievements

We have performed the analysis of personal genomics in the subfamily of Japanese patients with inflammatory bowel disease (IBD) and tried to identify the IBD-related single nucleotide variants (SNV) that are unique to the Japanese IBD patients, by conducting exome analysis of trio and affected siblings of several families with using the current methods. We completed the analysis of 3 families (related to IBD patients). In one family, polymorphisms in the promoter region associated with Th2 cytokine (IL-5 and IL-13) expression were observed. In other families, gene polymorphisms in the promoter region associated with IL-1 beta expression were observed.

Academic Significance and Societal Importance of the Research Achievements

IBDは原因不明の難治性炎症性疾患である。現在まで環境因子、遺伝的要素ならびに腸内細菌の異常に基づき、腸管内免疫寛容の破綻が生じた結果、IBDが発症すると考えられてきた。現在までの研究の多くが根本的な病態の解明につながるものではなく、IBD発症後の結果を解析しているものにすぎない。我々の研究結果から、IBD発症に関与する様々なSNPが存在することが明らかとなった。今後は個々の患者におけるサイトカイン産生など（自然免疫）に関連する遺伝子のSNPを見出すことで、IBD治療におけるpersonalized medicineを構築していく必要がある。

Research Products

• [Journal Article] Optimizing the Use of Current Treatments and Emerging Therapeutic Approaches to Achieve Therapeutic Success in Patients with Inflammatory Bowel Disease. (2019)
  • Author(s): Nakase H.
  • Journal Title: Gut Liver. Volume: 印刷中 Issue: 1 Pages: 7-19
  • DOI: 10.5009/gnl18203
  • Peer Reviewed / Open Access
• [Journal Article] Current clinical issue of skin lesions in patients with inflammatory bowel disease. (2019)
  • Author(s): Iida T, Hida T, Matsuura M, Uhara H, Nakase H.
  • Journal Title: Clin J Gastroenterol. Volume: 印刷中 Issue: 6 Pages: 501-510
  • DOI: 10.1007/s12328-019-00958-y
  • Peer Reviewed / Open Access
• [Journal Article] A Rare Cause of Ileus in a Middle-Aged Japanese Woman. (2019)
  • Author(s): Iida T, Arimura Y, Nakase H.
  • Journal Title: Clin Gastroenterol Hepatol. Volume: 印刷中 Issue: 4 Pages: e43-e43
  • DOI: 10.1016/j.cgh.2019.02.034
  • Peer Reviewed
• [Journal Article] Concerns and side effects of azathioprine during adalimumab induction and maintenance therapy for Japanese patients with Crohn's disease: a sub-analysis of a prospective randomized clinical trial (DIAMOND study). (2019)
  • Author(s): Hisamatsu T, Matsumoto T, Watanabe K,;Nakase H, Motoya S, Yoshimura N, Ishida T, Kato S, Nakagawa T, Esaki M, Nagahori M, Matsui T, Naito Y, Kanai T, Suzuki Y, Nojima M, Watanabe M, Hibi T; DIAMOND study group.
  • Journal Title: J Crohns Colitis. Volume: 印刷中 Issue: 9 Pages: 1097-1104
  • DOI: 10.1093/ecco-jcc/jjz030
  • Peer Reviewed / Open Access
• [Journal Article] Tumor recognition of peanut agglutinin-immobilized fluorescent nanospheres in biopsied human tissues. (2019)
  • Author(s): Kumagai H, Yamada K, Nakai K, Kitamura T, Mohri K, Ukawa M, Tomono T, Eguchi T, Yoshizaki T, Fukuchi T, Yoshino T, Matsuura M, Tobita E, Pham W ;Nakase H, Sakuma S.
  • Journal Title: Eur J Pharm Biopharm. Volume: 136 Pages: 29-37
  • DOI: 10.1016/j.ejpb.2019.01.007
  • Peer Reviewed / Open Access
• [Journal Article] OPeNing the Epithelial Barrier: Osteopontin Preserves Gut Barrier Function During Intestinal Inflammation. (2019)
  • Author(s): Nakase H.
  • Journal Title: Dig Dis Sci. Volume: 64 Issue: 2 Pages: 294-296
  • DOI: 10.1007/s10620-018-5350-7
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Autophagy of Innate Immune Cells on Inflammatory Bowel Disease. (2018)
  • Author(s): Iida T, Yokoyama Y, Wagatsuma K, Hirayama D, Nakase H.
  • Journal Title: Cells. Volume: 8 Issue: 1 Pages: 7-7
  • DOI: 10.3390/cells8010007
  • Peer Reviewed / Open Access
• [Journal Article] The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis. (2017)
  • Author(s): Hirayama D, Iida T, Nakase H.
  • Journal Title: Int J Mol Sci. Volume: 19 Issue: 1 Pages: 92-92
  • DOI: 10.3390/ijms19010092
  • Peer Reviewed / Open Access
• [Journal Article] Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: a subanalysis of the DIAMOND trial. (2017)
  • Author(s): Nakase H, Motoya S, Matsumoto T, Watanabe K, Hisamatsu T, Yoshimura N, Ishida T, Kato S, Nakagawa T, Esaki M, Nagahori M, Matsui T, Naito Y, Kanai T, Suzuki Y, Nojima M, Watanabe M, Hibi T; DIAMOND study group.
  • Journal Title: Aliment Pharmacol Ther. Volume: 46 Issue: 9 Pages: 873-882
  • DOI: 10.1111/apt.14318
  • Peer Reviewed / Open Access
• [Journal Article] A Unique Cause of Persistent Diarrhea. (2017)
  • Author(s): Iida T, Yamashita K, Nakase H.
  • Journal Title: Gastroenterology. Volume: 152 Issue: 6 Pages: 1291-1292
  • DOI: 10.1053/j.gastro.2016.11.051
  • Peer Reviewed
• [Journal Article] Evaluation of a novel fluorescent nanobeacon for targeted imaging of Thomsen-Friedenreich associated colorectal cancer. (2017)
  • Author(s): Nakase H, Sakuma S, Fukuchi T, Yoshino T, Mohri K, Miyata K, Kumagai H, Hiwatari KI, Tsubaki K, Ikejima T, Tobita E, Zhu M, Wilson KJ, Washington K, Gore JC, Pham W.
  • Journal Title: Int J Nanomedicine. Volume: 12 Pages: 1747-1755
  • DOI: 10.2147/ijn.s124174
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Osteopontin attenuates acute gastrointestinal graft-versus-host disease by preventing apoptosis of intestinal epithelial cells. (2017)
  • Author(s): Kawakami K, Minami N, Matsuura M, Iida T, Toyonaga T, Nagaishi K, Arimura Y, Fujimiya M, Uede T, Nakase H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 485 Issue: 2 Pages: 468-475
  • DOI: 10.1016/j.bbrc.2017.02.047
  • Peer Reviewed / Open Access
• [Presentation] パーソナルゲノム解析を通じた日本人クローン病感受性遺伝子の探索 (2016)
  • Author(s): 小野寺 馨, 有村 佳昭, 榮浪 洋介, 横山 佳浩, 山本 至, 一色 裕之, 川上 賢太郎, 久保 俊之, 山下 健太郎, 仲瀬 裕志
  • Organizer: 第24回日本消化器関連学会週間（JDDW）
  • Place of Presentation: 神戸コンベンションセンター