A new mechanism of intestinal inflammation based on copy number polymorphism

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07918
• 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: Kagoshima University
• Principal Investigator: Kanmura Shuji 鹿児島大学, 医歯学域鹿児島大学病院, 准教授 (60448561)
• Co-Investigator(Kenkyū-buntansha): 熊谷 公太郎 鹿児島大学, 医歯学域鹿児島大学病院, 助教 (80626664) ; 田中 啓仁 鹿児島大学, 鹿児島大学病院, 医員 (90896127)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Defensin alpha / 好中球ペプチド / 潰瘍性大腸炎 / コピー数多型

Outline of Final Research Achievements

Copy number variations (CNVs) of defensin alpha (DEFA) 1-3 have been implicated in the pathogenesis of autoimmune diseases, the association between DEFA1A3-CNVs and ulcerative colitis (UC) is unknown. In this study, DEFA1A3 copy number and clinical activity were correlated in patients with UC. In a multivariate analysis, DEFA1A3 high copy number was an independent factor determining clinical severity. On the other hand, in neutrophil-specific DEFA1A3-transgenic (Tg) mice, high copy number Tg mice also showed a significantly higher mortality rate from DSS colitis and a higher clinical activity and histological scores of colitis compared to wild-type mice.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

本研究はこれまで報告のない潰瘍性大腸炎における重症度とDEFA1A3-CNVの関連性に着目した新しいバイオマーカー探索の研究である。DEFA1A3コピー数の測定は，潰瘍性大腸炎患者個々人における，治療反応性や重症化の予測マーカーの開発につながり，極めて臨床的にも意義深い。この研究の発展させることができれば，不要なリスクを冒すことなく適切な治療を選択できるような医療を提供できる社会の実現が期待できる。