Genetic background associated with treatments for Japanese patients with ulcerative colitis

• Project/Area Number: 18K15740
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tohoku University
• Principal Investigator: Onodera Motoyuki 東北大学, 医学系研究科, 大学院非常勤講師 (90816224)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 潰瘍性大腸炎 / 薬理ゲノム / 疾患感受性遺伝子 / メサラジン / ゲノムワイド相関解析 / 炎症性腸疾患 / 疾患修飾遺伝子

Outline of Final Research Achievements

Phenotypes of ulcerative colitis are varies from patients, and responses to each treatment are also different. Therefore, it is important to investigate the genetic background associated with responses to treatment for ulcerative colitis. In this study, we have identified that the SNPs located in the HLA regions which is associated with the onset of ulcerative colitis in Japanese were also associated with good prognosis. Additionally, 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). 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%).

Academic Significance and Societal Importance of the Research Achievements

本研究は、多彩な病態を示す潰瘍性大腸炎の治療戦略において、遺伝的背景を考慮することの重要性を示唆するものであり、将来の個別化医療における遺伝子情報の有用性を明らかにしている。現在、潰瘍性大腸炎の新規治療薬が次々と実用化されてきているが、それぞれの治療有効性は決して高いものではなく、効果がある薬剤を探しながら順に使用している流れであるが、遺伝情報を活用することで、その優先順位などを考慮し、より効率的かつ安全に治療を行うことが可能となる。また、効率的・安全な治療は、不必要な治療を回避することで医療経済的な効果があることから、本研究結果などをもとにあらたな治療モデルの構築につながる可能性がある。

Research Products

• [Journal Article] Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease (2021)
  • Author(s): Suzuki K, Kakuta Y, Naito T, Takagawa T, Hanai H, Araki H, Sasaki Y, Sakuraba H, Sasaki M, Hisamatsu T, Motoya S, Matsumoto T, Onodera M, Ishiguro Y, Nakase H, et al.
  • Journal Title: Inflamm Bowel Dis Volume: - Issue: 1 Pages: 21-31
  • DOI: 10.1093/ibd/izab004
  • Peer Reviewed / Int'l Joint Research