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20231226053835.0 |
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231226s2023 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2023.109250
|2 doi
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|a pubmed24n1174.xml
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|a (DE-627)NLM35248831X
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|a (NLM)36738816
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|a (PII)S1521-6616(23)00029-3
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Liu, Yu
|e verfasserin
|4 aut
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| 245 |
1 |
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|a DNA methylation of ITGB2 contributes to allopurinol hypersensitivity
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|c 2023
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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| 338 |
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 14.03.2023
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|a Date Revised 18.03.2023
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2023 Elsevier Inc. All rights reserved.
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|a BACKGROUNDS: HLA-B*58:01 allele was strongly associated with allopurinol induced severe cutaneous adverse drug reaction (SCAR). However, HLA-B genotype is not sufficient to predict the occurrence of allopurinol-induced SCAR
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|a OBJECTIVE: To discover DNA methylation markers for allopurinol-induced SCAR which may improve the prediction accuracy of genetic testing
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|a STUDY DESIGN: The study was designed as a retrospective case-control clinical study in multicenter hospitals across Taiwan, Mainland China, Malaysia and Canada. 125 cases of allopurinol-induced SCAR patients and 139 cases of allopurinol tolerant controls were enrolled in this study during 2005 to 2021
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|a RESULTS: The results of genome-wide DNA methylation assay of 62 patients revealed that ITGB2 showed strong discriminative ability of allopurinol-induced SCAR in both HLA-B*58:01 positive and negative patients with AUC value of 0.9364 (95% CI 0.8682-1.000). In validation study, significant hypermethylation of ITGB2 were further validated in allopurinol-induced SCAR patients compared to tolerant controls, especially in those without HLA-B*58:01(AUC value of 0.8814 (95% CI 0.7121-1.000)). Additionally, the methylation levels of 2 sites on ITGB2 were associated with SCAR phenotypes. Combination of HLA-B*58:01 genotyping and ITGB2 methylation status could improve the prediction accuracy of allopurinol-induced SCAR with the AUC value up to 0.9387 (95% CI 0.9089-0.9684), while the AUC value of HLA-B*58:01 genotyping alone was 0.8557 (95% CI 0.8030-0.9083)
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|a CONCLUSIONS: Our study uncovers differentially methylated genes between allopurinol-induced SCAR patients and tolerant controls with positive or negative HLA-B*58:01 allele and provides the novel epigenetic marker that improves the prediction accuracy of genetic testing for prevention of allopurinol-induced SCAR
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|a Multicenter Study
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a Allopurinol
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| 650 |
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|a Drug hypersensitivity
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| 650 |
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|a Genome-wide DNA methylation
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| 650 |
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|a HLA-B*58:01
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| 650 |
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4 |
|a ITGB2
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| 650 |
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|a Severe cutaneous adverse drug reaction
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| 650 |
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7 |
|a Allopurinol
|2 NLM
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| 650 |
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7 |
|a 63CZ7GJN5I
|2 NLM
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| 650 |
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7 |
|a HLA-B Antigens
|2 NLM
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| 700 |
1 |
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|a Wang, Chuang-Wei
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Chen, Chun-Bing
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yu, Kuang-Hui
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wu, Yeong-Jian
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Choon, Siew-Eng
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Chang, Wan-Chun
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yang, Fanping
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Luo, Xiao-Qun
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Chung, Wen-Hung
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhao, Ming
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Lu, Qian-Jin
|e verfasserin
|4 aut
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| 773 |
0 |
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|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 248(2023) vom: 05. März, Seite 109250
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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| 773 |
1 |
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|g volume:248
|g year:2023
|g day:05
|g month:03
|g pages:109250
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| 856 |
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|u http://dx.doi.org/10.1016/j.clim.2023.109250
|3 Volltext
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