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Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations
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:...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675242/ https://www.ncbi.nlm.nih.gov/pubmed/34925040 http://dx.doi.org/10.3389/fphar.2021.784712 |
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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 |
author_facet | 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 |
author_sort | Khaeso, Kanyarat |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8675242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86752422021-12-17 Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations 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 Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2021-12-02 /pmc/articles/PMC8675242/ /pubmed/34925040 http://dx.doi.org/10.3389/fphar.2021.784712 Text en Copyright © 2021 Khaeso, Udayachalerm, Komvilaisak, Chainansamit, Suwannaying, Laoaroon, Kuwatjanakul, Nakkam, Sukasem, Puangpetch, Tassaneeyakul and Chaiyakunapruk. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology 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 Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations |
title | Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations |
title_full | Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations |
title_fullStr | Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations |
title_full_unstemmed | Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations |
title_short | Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations |
title_sort | meta-analysis of nudt15 genetic polymorphism on thiopurine-induced myelosuppression in asian populations |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675242/ https://www.ncbi.nlm.nih.gov/pubmed/34925040 http://dx.doi.org/10.3389/fphar.2021.784712 |
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