Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations.

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.

• Authors: Kanyarat Khaeso, Sariya Udayachalerm, Patcharee Komvilaisak, Su-On Chainansamit, Kunanya Suwannaying, Napat Laoaroon, Pitchayanan Kuwatjanakul, Nontaya Nakkam, Chonlaphat Sukasem, Apichaya Puangpetch, Wichittra Tassaneeyakul, Nathorn Chaiyakunapruk
• Journal: Frontiers in pharmacology (Front Pharmacol) Vol. 12 Pg. 784712 ( 2021) ISSN: 1663-9812 [Print] Switzerland
• PMID: 34925040 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2021 Khaeso, Udayachalerm, Komvilaisak, Chainansamit, Suwannaying, Laoaroon, Kuwatjanakul, Nakkam, Sukasem, Puangpetch, Tassaneeyakul and Chaiyakunapruk.