Precision medicine using NUDT15 variant for thiopurine therapy in inflammatory bowel diseases

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08976
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hyogo Medical University
• Principal Investigator: Nakamura Shiro 兵庫医科大学, 医学部, 教授 (50271185)
• Co-Investigator(Kenkyū-buntansha): 高川 哲也 兵庫医科大学, 医学部, 助教 (20444614)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: NUDT15 / 炎症性腸疾患 / 潰瘍性大腸炎 / クローン病 / チオプリン / 個別化医療 / 遺伝子多型

Outline of Final Research Achievements

Thiopurines are generally used for the treatment of inflammatory bowel diseases (IBD), but induce adverse events (AEs) including severe hair loss and early leukopenia. The causes of those AEs in Japanese IBD patients remain unknown. In 2014, it was reported that NUDT15 genetic variant was strongly associated with those AEs in Korean IBD patients. Therefore, we investigated whether this association could be replicated in Japanese and how this gene was involved in thiopurine-induced cell death. In this study, we could replicate the strong associations, and found that the carriers of risk allele in NUDT15 gene could be followed up with lower dose of thiopurine and better clinical efficacy than those of non-risk allele. We generated NUDT15 deficient cells to investigate the molecular mechanisms of thiopurine-induced cell death, and found that this genetic variant might induce loss of function of NUDT15. NUDT15 is a promising genetic marker for the prediction of thiopurine-induced AEs.

Free Research Field

炎症性腸疾患