Objective  To systematically evaluate the association of NUDT15 gene polymorphism with thiopurine-induced leukopenia.

Methods  Relevant articles were searched electronically from CNKI, WanFang Data, VIP, CBM, PubMed and Embase from inception of the databases to June 2023. The quality of the included articles was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS), a Meta-analysis was conducted by Stata 14.0 software.

Results  Seventeen articles involving 4 057 patients were included. Among them, 1 017 patients developed leukopenia or neutropenia in varying degrees after using thiopurine drugs.

Results of Meta-analysis showed that the overall effects of each group were statistically significant (P<0.001) under the NUDT15 gene polymorphism: for the leukopenia caused by medication within 8 weeks, the allele model [OR= 0.15, 95%CI (0.10, 0.22), P<0.001], the dominant gene model [OR = 0.13, 95%CI (0.08, 0.20), P<0.001], and the heterozygous gene model [OR = 0.04, 95%CI (0.01, 0.19), P<0.001] were statistically associated with leukopenia; for the leukopenia after 8 weeks, the allele model [OR= 0.18, 95%CI (0.11, 0.30), P<0.001], the dominant gene model [OR = 0.17, 95%CI (0.09, 0.31), P<0.001], the heterozygous gene model [OR = 0.05, 95%CI (0.02, 0.15), P<0.001] were statistically associated with leukopenia; for the grade 3 to 4 severe leukopenia, the dominant gene model [OR=0.09, 95%CI (0.05, 0.15), P<0.001] was statistically associated with leukopenia.

Conclusion  The polymorphism of NUDT15 gene was associated with leukopenia induced by thiopurines.

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