AUTHOR=Khaeso Kanyarat , Udayachalerm Sariya , Komvilaisak Patcharee , Chainansamit Su-on , Suwannaying Kunanya , Laoaroon Napat , Kuwatjanakul Pitchayanan , Nakkam Nontaya , Sukasem Chonlaphat , Puangpetch Apichaya , Tassaneeyakul Wichittra , Chaiyakunapruk Nathorn 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.784712

DOI=10.3389/fphar.2021.784712

ISSN=1663-9812

ABSTRACT=<p><bold>Backgound:</bold> 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.</p><p><bold>Methods:</bold> 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 <italic>NUDT15</italic> and the risk of thiopurine-induced myelosuppression stratified by onset and type of myelosuppressive. Subgroup analysis by <italic>NUDT15</italic> genetic polymorphisms was performed.</p><p><bold>Results:</bold> A total of 30 studies was included in this meta-analysis. The overall OR for the relationship between <italic>NUDT15</italic> 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 <italic>NUDT15</italic> polymorphisms, <italic>NUDT15*3</italic> 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 <italic>NUDT15*2</italic> (OR 37.51; 95% CI 1.99–708.69)<italic>.</italic> Whereas, <italic>NUDT15*5</italic> and <italic>NUDT15*6</italic> variants showed a lower risk of leukopenia.</p><p><bold>Conclusion:</bold> This study suggests that <italic>NUDT15*3</italic> and <italic>NUDT15*2</italic> 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.</p>