Associations between the NUDT15 R139C polymorphism and susceptibility to thiopurine-induced leukopenia in Asians: a meta-analysis

BACKGROUND AND AIM: Despite several studies being conducted to examine the associations between the NUDT15 R139C polymorphism and thiopurine-induced leukopenia in the Asian population, the results remain inconsistent. This meta-analysis determined the risk of thiopurine-induced leukopenia conferred by the NUDT15 R139C polymorphism. MATERIALS AND METHODS: All eligible studies published in English up to May 2018 were identified by searching PubMed, Web of Science, Embase, and the Cochrane Library. Pooled OR and 95% CI were calculated using fixed- or random-effect model. RESULTS: In all, total of 14 studies containing 918 patients and 2,341 controls were included; of these, 8 studies concerned inflammatory bowel disease (IBD) and 4 concerned acute lymphoblastic leukemia (ALL). Overall, the results indicated that the NUDT15 R139C polymorphism was associated with leukopenia induced by thiopurines (OR =9.04, 95% CI 6.05–13.50, P<0.001 for the dominant model; OR =24.26, 95% CI 11.38–51.71, P<0.001 for the recessive model; OR =7.60, 95% CI 4.97–11.61, P<0.001 for the CT vs TT model; OR =38.47, 95% CI 17.78–83.24, P<0.001 for the CC vs TT model). In subgroup analyses, significant associations were found among patients with IBD (OR =7.57, 95% CI 5.16–11.12, P<0.001 for the dominant model), ALL (OR =13.13, 95% CI 3.43–50.23 P<0.001 for the dominant model), and other diseases (OR =31.22, 95% CI 1.20–814.07, P=0.04 for the dominant model). In addition, the R139C variant was strongly associated with early (<8 weeks) (OR =15.53, 95% CI 7.91–30.50, P<0.001 for the dominant model) and late leukopenia (≥8 weeks) (OR =2.92, 95% CI 2.01–4.24, P<0.001 for the dominant model). Moreover, these findings were sufficiently robust when studies without Hardy–Weinberg equilibrium test were excluded. CONCLUSION: This meta-analysis verified the strong association between the NUDT15 R139C polymorphism and thiopurine-induced leukopenia (both early and late leukopenia) in an Asian population with IBD, ALL, and other diseases. NUDT15 R139C genotyping should be prioritized to predict leukopenia among Asians.