| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| 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.
|
