Objective:To analyze the association between NUDT15 gene polymorphism and adverse reactions induced by azathioprine (AZA) myelosuppression in patients with inflammatory bowel disease (IBD) , and to provide reference for clinical treatment of IBD. Methods:Literatures of randomized controlled trials of NUDT15 gene mutation and AZA in the treatment of IBD were searched with computer from China Knowledge Network, Wanfang database, VIP database, PubMed, Cochrane Library and Web of Science. The quality evaluation and data of studies meeting the inclusion criteria were screened and retrieved to perform meta analysis. Results:Ten literatures were enrolled including 3095 patients. Meta analysis showed that the mutation rate of NUDT15 gene in Asian IBD population was significantly higher than that of TPMT gene (21.5% vs. 2.8%, OR = 0.10, 95% CI: 0.07-0.15, P<0.001) with significant difference. NUDT15 gene mutation was significantly associated with AZA-related leukopenia ( OR = 0.40, 95% CI: 0.34-0.47, P<0.001) . IBD patients with NUDT15 mutation were more likely to develop leukopenia in the early stage of AZA application ( OR = 2.69, 95% CI: 1.67-4.33, P<0.001) . Besides, homozygous mutants of NUDT15 gene (TT type) were more likely to have grade Ⅲ-Ⅳ bone marrow suppression ( OR = 0.09, 95% CI: 0.04-0.18, P<0.001) . Conclusions:In Asian IBD population, bone marrow suppression caused by AZA is significantly associated with NUDT15 gene mutation, which is more closely associated than TPMT gene mutation and usually occurs within 8 weeks of AZA application. At the same time, homozygous mutations of NUDT15 gene (TT) increase the risk of severe myelosuppression.

Objective:To analyze the association between NUDT15 gene polymorphism and adverse reactions induced by azathioprine (AZA) myelosuppression in patients with inflammatory bowel disease (IBD) , and to provide reference for clinical treatment of IBD. Methods:Literatures of randomized controlled trials of NUDT15 gene mutation and AZA in the treatment of IBD were searched with computer from China Knowledge Network, Wanfang database, VIP database, PubMed, Cochrane Library and Web of Science. The quality evaluation and data of studies meeting the inclusion criteria were screened and retrieved to perform meta analysis. Results:Ten literatures were enrolled including 3095 patients. Meta analysis showed that the mutation rate of NUDT15 gene in Asian IBD population was significantly higher than that of TPMT gene (21.5% vs. 2.8%, OR = 0.10, 95% CI: 0.07-0.15, P<0.001) with significant difference. NUDT15 gene mutation was significantly associated with AZA-related leukopenia ( OR = 0.40, 95% CI: 0.34-0.47, P<0.001) . IBD patients with NUDT15 mutation were more likely to develop leukopenia in the early stage of AZA application ( OR = 2.69, 95% CI: 1.67-4.33, P<0.001) . Besides, homozygous mutants of NUDT15 gene (TT type) were more likely to have grade Ⅲ-Ⅳ bone marrow suppression ( OR = 0.09, 95% CI: 0.04-0.18, P<0.001) . Conclusions:In Asian IBD population, bone marrow suppression caused by AZA is significantly associated with NUDT15 gene mutation, which is more closely associated than TPMT gene mutation and usually occurs within 8 weeks of AZA application. At the same time, homozygous mutations of NUDT15 gene (TT) increase the risk of severe myelosuppression.