Genetic Polymorphisms of Drug-Metabolizing Enzymes Involved in 6-Mercaptopurine-Induced Myelosuppression in Thai Pediatric Acute Lymphoblastic Leukemia Patients

Khaeso, Kanyarat; Nakkam, Nontaya; Komwilaisak, Patcharee; Wongmast, Piyathida; Chainansamit, Su-on; Dornsena, Areerat; Kanjanawart, Sirimas; Vannaprasaht, Suda; Tassaneeyakul, Wichittra

doi:10.1055/s-0040-1715818

Cited by 3 publications

(1 citation statement)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, more than 20 variants of the NUDT15 gene have been reported ( Yang et al, 2019b ). The common variant alleles are NUDT15*2 (rs869320766; c.36_37insGGAGTC and rs116855232; c.415C > T), NUDT15*3 (rs116855232; c.415C > T), NUDT15*5 (rs186364861; c.52G > A), and NUDT15*6 (rs869320766; c.36_37insGGAGTC) ( Moriyama et al, 2016 ) in which NUDT13*3 is the most prevalent in Asian populations ( Yang et al, 2014 ; Yang et al, 2015 ; Moriyama et al, 2016 ; Kim et al, 2017a ; Khaeso et al, 2021 ). This current study’s results indicate that the overall OR for the relationship between NUDT15 genetic polymorphisms and thiopurine-induced early onset of leukopenia and neutropenia were 11.43 (95%CI 7.11–18.35) and 16.35 (95% CI 10.20–26.22).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

Detailed resume of S-methyltransferases: Categories, structures, biological functions and research advancements in related pathophysiology and pharmacotherapy

Mu,

Ye,

Wang

2024

Biochemical Pharmacology

View full text Add to dashboard Cite

NUDT15Genotyping in Thiopurine Drug Therapy

2022

View full text Add to dashboard Cite

Thiopurine is a pro-drug used to treat patients with inflammatory bowel disease, leukemia, malignancies, and autoimmune diseases as well as an immunosuppressive agent for post-transplantation states. Thiopurine drugs are metabolized into active metabolites by enzymes in various metabolic stages in the body. The importance of NUDT15 genotyping is emerging in the literature and clinical guidelines since it has been found to be associated with fatal thiopurine-related adverse drug reactions such as cytopenia, hepatotoxicity, and hair loss. Therefore, this review provides practical information about the clinical pharmacogenetic test for NUDT15 in patients treated with thiopurines to assist clinical laboratories in Korea. It focuses on thiopurine drug metabolism, clinical implications, and of NUDT15 genotyping. Moreover, it considers reports of pharmacogenetic test results, including current recommendations on NUDT15-guided thiopurine dosing.

show abstract

Genetic Polymorphisms of Drug-Metabolizing Enzymes Involved in 6-Mercaptopurine-Induced Myelosuppression in Thai Pediatric Acute Lymphoblastic Leukemia Patients

Cited by 3 publications

References 35 publications

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

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

Detailed resume of S-methyltransferases: Categories, structures, biological functions and research advancements in related pathophysiology and pharmacotherapy

NUDT15Genotyping in Thiopurine Drug Therapy

Contact Info

Product

Resources

About