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:...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-12-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.784712/full |
| _version_ | 1818981933255753728 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T17:39:11Z |
| format | Article |
| id | doaj.art-0b802fac302c4255b3dc0f00f3ef8768 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T17:39:11Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-0b802fac302c4255b3dc0f00f3ef87682022-12-21T19:31:09ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-12-011210.3389/fphar.2021.784712784712Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian PopulationsKanyarat Khaeso0Sariya Udayachalerm1Patcharee Komvilaisak2Su-on Chainansamit3Kunanya Suwannaying4Napat Laoaroon5Pitchayanan Kuwatjanakul6Nontaya Nakkam7Chonlaphat Sukasem8Chonlaphat Sukasem9Apichaya Puangpetch10Apichaya Puangpetch11Wichittra Tassaneeyakul12Nathorn Chaiyakunapruk13Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, United StatesDepartment of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Pediatrics, Khon Kaen Hospital, Khon Kaen, ThailandDepartment of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Pediatrics, Udon Thani Hospital, Udon Thani, ThailandDepartment of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDivision of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandLaboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, ThailandDivision of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandLaboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, ThailandDepartment of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, ThailandDepartment of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, United StatesBackgound: 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.784712/fullnucleoside diphosphate–linked moiety X-type motif 15 (NUDT15)thiopurine drugshematotoxicitygenetic polymorphismprecision medicineMeta-analysis |
| spellingShingle | 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 Frontiers in Pharmacology nucleoside diphosphate–linked moiety X-type motif 15 (NUDT15) thiopurine drugs hematotoxicity genetic polymorphism precision medicine Meta-analysis |
| 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 | nucleoside diphosphate–linked moiety X-type motif 15 (NUDT15) thiopurine drugs hematotoxicity genetic polymorphism precision medicine Meta-analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.784712/full |
| work_keys_str_mv | AT kanyaratkhaeso metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT sariyaudayachalerm metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT patchareekomvilaisak metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT suonchainansamit metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT kunanyasuwannaying metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT napatlaoaroon metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT pitchayanankuwatjanakul metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT nontayanakkam metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT chonlaphatsukasem metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT chonlaphatsukasem metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT apichayapuangpetch metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT apichayapuangpetch metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT wichittratassaneeyakul metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations AT nathornchaiyakunapruk metaanalysisofnudt15geneticpolymorphismonthiopurineinducedmyelosuppressioninasianpopulations |