DNA methylation of ITGB2 contributes to allopurinol hypersensitivity.
Clin Immunol
; 248: 109250, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36738816
ABSTRACT
BACKGROUNDS HLA-B*5801 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. OBJECTIVE:
To discover DNA methylation markers for allopurinol-induced SCAR which may improve the prediction accuracy of genetic testing. STUDYDESIGN:
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.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*5801 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*5801(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*5801 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*5801 genotyping alone was 0.8557 (95% CI 0.8030-0.9083).CONCLUSIONS:
Our study uncovers differentially methylated genes between allopurinol-induced SCAR patients and tolerant controls with positive or negative HLA-B*5801 allele and provides the novel epigenetic marker that improves the prediction accuracy of genetic testing for prevention of allopurinol-induced SCAR.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Síndrome de Stevens-Johnson
/
Hipersensibilidade a Drogas
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article