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:...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	nucleoside diphosphate–linked moiety X-type motif 15 (NUDT15) thiopurine drugs hematotoxicity genetic polymorphism precision medicine Meta-analysis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/0b802fac302c4255b3dc0f00f3ef8768
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spelling	oai:doaj.org-article:0b802fac302c4255b3dc0f00f3ef87682021-12-02T11:20:34ZMeta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations1663-981210.3389/fphar.2021.784712https://doaj.org/article/0b802fac302c4255b3dc0f00f3ef87682021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.784712/fullhttps://doaj.org/toc/1663-9812Backgound: 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, NUDT153 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 NUDT152 (OR 37.51; 95% CI 1.99–708.69). Whereas, NUDT155 and NUDT156 variants showed a lower risk of leukopenia.Conclusion: This study suggests that NUDT153 and NUDT152 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.Kanyarat KhaesoSariya UdayachalermPatcharee KomvilaisakSu-on ChainansamitKunanya SuwannayingNapat LaoaroonPitchayanan KuwatjanakulNontaya NakkamChonlaphat SukasemChonlaphat SukasemApichaya PuangpetchApichaya PuangpetchWichittra TassaneeyakulNathorn ChaiyakunaprukFrontiers Media S.A.articlenucleoside diphosphate–linked moiety X-type motif 15 (NUDT15)thiopurine drugshematotoxicitygenetic polymorphismprecision medicineMeta-analysisTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nucleoside diphosphate–linked moiety X-type motif 15 (NUDT15) thiopurine drugs hematotoxicity genetic polymorphism precision medicine Meta-analysis Therapeutics. Pharmacology RM1-950
spellingShingle	nucleoside diphosphate–linked moiety X-type motif 15 (NUDT15) thiopurine drugs hematotoxicity genetic polymorphism precision medicine Meta-analysis Therapeutics. Pharmacology RM1-950 Kanyarat Khaeso Sariya Udayachalerm Patcharee Komvilaisak Su-on Chainansamit Kunanya Suwannaying Napat Laoaroon Pitchayanan Kuwatjanakul Nontaya Nakkam Chonlaphat Sukasem Chonlaphat Sukasem Apichaya Puangpetch Apichaya Puangpetch Wichittra Tassaneeyakul Nathorn Chaiyakunapruk Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations
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, NUDT153 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 NUDT152 (OR 37.51; 95% CI 1.99–708.69). Whereas, NUDT155 and NUDT156 variants showed a lower risk of leukopenia.Conclusion: This study suggests that NUDT153 and NUDT152 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	article
author	Kanyarat Khaeso Sariya Udayachalerm Patcharee Komvilaisak Su-on Chainansamit Kunanya Suwannaying Napat Laoaroon Pitchayanan Kuwatjanakul Nontaya Nakkam Chonlaphat Sukasem Chonlaphat Sukasem Apichaya Puangpetch Apichaya Puangpetch Wichittra Tassaneeyakul Nathorn Chaiyakunapruk
author_facet	Kanyarat Khaeso Sariya Udayachalerm Patcharee Komvilaisak Su-on Chainansamit Kunanya Suwannaying Napat Laoaroon Pitchayanan Kuwatjanakul Nontaya Nakkam Chonlaphat Sukasem Chonlaphat Sukasem Apichaya Puangpetch Apichaya Puangpetch Wichittra Tassaneeyakul Nathorn Chaiyakunapruk
author_sort	Kanyarat Khaeso
title	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_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_sort	meta-analysis of nudt15 genetic polymorphism on thiopurine-induced myelosuppression in asian populations
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0b802fac302c4255b3dc0f00f3ef8768
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Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations

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