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Publication
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Title of Article |
Meta-analysis of NUDT15 genetic polymorphism on thiopurineinduced myelosuppression in Asian populations |
Date of Acceptance |
16 November 2021 |
Journal |
Title of Journal |
Frontiers in Pharmacology |
Standard |
SCOPUS |
Institute of Journal |
Frontiers Media SA |
ISBN/ISSN |
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Volume |
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Issue |
12 |
Month |
December |
Year of Publication |
2021 |
Page |
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Abstract |
Backgound: The high incidence of thiopurine-induced myelosuppression in Asians is known to be attributable to genetic variation in thiopurine metabolism. A quantitative synthesis to summarize the genetic association with thiopurine-induced myelosuppression in Asians was therefore conducted.
Methods: A Literature search was performed from January 2016 to May 2021 in the following databases: PubMed, Web of Science, and Embase and addition search included the studies from Zhang et al. Two reviewers independently extracted the following data: the author’s name, year of publication, ethnicity, drugs, diseases, genetic polymorphisms, onset, type of myelosuppression and results of Hardy-Weinberg equilibrium. The Newcastle-Ottawa Scale was used to assess the quality of the studies. The pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations of NUDT15 and the risk of thiopurine-induced myelosuppression stratified by onset and type of myelosuppressive. Subgroup analysis by NUDT15 genetic polymorphisms was performed.
Results: A total of 30 studies was included in this meta-analysis. The overall OR for the relationship between NUDT15 genetic polymorphisms and thiopurine-induced early onset of leukopenia and neutropenia in Asian populations were 11.43 (95% CI 7.11–18.35) and 16.35 (95% CI 10.20–26.22). Among NUDT15 polymorphisms, NUDT15*3 showed a significantly increased risk of early leukopenia (OR 15.31; 95% CI 9.65–24.27) and early neutropenia (OR 15.85; 95% CI 8.80–28.53). A significantly higher thiopurine-induced early neutropenic risk was also found for NUDT15*2 (OR 37.51; 95% CI 1.99–708.69). Whereas, NUDT15*5 and NUDT15*6 variants showed a lower risk of leukopenia.
Conclusion: This study suggests that NUDT15*3 and NUDT15*2 are important genetic markers of thiopurine-induced early onset of myelotoxicity in Asians, therefore, early detection of these variants before initiating thiopurine therapy is necessary. |
Keyword |
nucleoside diphosphate–linked moiety X-type motif 15 (NUDT15), thiopurine drugs, hematotoxicity, genetic polymorphism, precision medicine, Meta-analysis, Systematic review |
Author |
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Reviewing Status |
มีผู้ประเมินอิสระ |
Status |
ตีพิมพ์แล้ว |
Level of Publication |
นานาชาติ |
citation |
true |
Part of thesis |
true |
Attach file |
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Citation |
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