Analysis of the Onset and Pathological Changes of Crohn's Disease through Somatic Mosaicism Mediated by Genomic Instability

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07955
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tohoku University
• Principal Investigator: Kakuta Yoichi 東北大学, 医学系研究科, 講師 (50509205)
• Co-Investigator(Kenkyū-buntansha): 木内 喜孝 東北大学, 高度教養教育・学生支援機構, 教授 (20250780) ; 黒羽 正剛 東北大学, 医学系研究科, 大学院非常勤講師 (70709469)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 炎症性腸疾患 / モザイク変異 / 染色体異常

Outline of Final Research Achievements

We conducted a genomic analysis of mosaic chromosomal abnormalities (mCA) in the blood of 3,339 Japanese patients with inflammatory bowel disease (IBD) to investigate their frequency, genetic background, and clinical data. The results indicated that the incidence of mCA was significantly higher in patients with Crohn's disease (CD) compared to those with ulcerative colitis (UC), with notable abnormalities observed particularly on chromosomes 3 and 6. mCA was identified as an independent risk factor for CD, unrelated to age or other clinical factors. The use of thiopurines at a young age increased the risk of mCA. Specifically, genes related to mucosal immune responses were enriched, involving processes such as "defense response to bacteria," "mucosal innate immune response," and "antimicrobial humoral immune response mediated by antimicrobial peptides." Further investigation is needed to determine whether the factors associated with the occurrence of mCA are causative or resultant.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

この研究の学術的意義として、クローン病（CD）患者におけるモザイク染色体異常（mCA）の高発生率と特定の染色体異常を世界で初めて明らかにしたことである。また、mCAがCDの独立したリスク因子であり、若年期のチオプリン使用がリスクを増加させることを示した。これにより、粘膜免疫応答に関連する遺伝子の関与が示唆され、CDの病態解明に貢献する。
また、社会的にはCD患者の治療方針に影響を与える。特に、若年患者へのチオプリン使用のリスク評価が重要であり、適切な治療戦略の立案に寄与する。さらに、CD患者に対する早期の診断と治療法の改善に繋がり、患者の生活の質向上が期待される。