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

Abstract

Background and aimDespite 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 methodsAll 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.ResultsIn 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.ConclusionThis 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.