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Aspirin Challenge–Induced Genome-Wide DNA Methylation Profile of Peripheral Blood Lymphocytes in Aspirin-Exacerbated Respiratory Disease

Title
Aspirin Challenge–Induced Genome-Wide DNA Methylation Profile of Peripheral Blood Lymphocytes in Aspirin-Exacerbated Respiratory Disease
Authors
LeeJong-UkChangHun SooShimJi-SuKimMin-HyeChoYoung-JooMin KyungParkSeung-LeeSun JuJong-SookChoon-Sik
Ewha Authors
조영주김민혜심지수
SCOPUS Author ID
조영주scopusscopus; 김민혜scopus; 심지수scopus
Issue Date
2024
Journal Title
DNA and Cell Biology
ISSN
1044-5498JCR Link
Citation
DNA and Cell Biology vol. 43, no. 3, pp. 132 - 140
Keywords
aspirin-exacerbated respiratory diseaseDNA CpG methylationIntroductionlymphocytes
Publisher
Mary Ann Liebert Inc.
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Genetic variation and epigenetic factors are thought to contribute to the development of hypersensitivity to aspirin. DNA methylation fluctuates dynamically throughout the day. To discover new CpG methylation in lymphocytes associated with aspirin-exacerbated respiratory disease (AERD), we evaluated changes in global CpG methylation profiles from before to after an oral aspirin challenge in patients with AERD and aspirin-tolerant asthma (ATA). Whole-genome CpG methylation levels of peripheral blood mononuclear cells were quantified with an Illumina 860K Infinium Methylation EPIC BeadChip array and then adjusted for inferred lymphocyte fraction (ILF) with GLINT and Tensor Composition Analysis. Among the 866,091 CpGs in the array, differentially methylated CpGs (DMCs) were found in 6 CpGs in samples from all 12 patients with asthma included in the study (AERD, n = 6; ATA, n = 6). DMCs were found in 3 CpGs in the 6 ATA samples and in 615 CpGs in the 6 AERD samples. A total of 663 DMCs in 415 genes and 214 intergenic regions differed significantly in the AERD compared with the ATA. In promoters, 126 CpG loci were predicted to bind to 38 transcription factors (TFs), many of which were factors already known to be involved in the pathogenesis of asthma and immune responses. In conclusion, we identified 615 new CpGs methylated in peripheral blood lymphocytes by oral aspirin challenge in AERD but not in ATA. These findings indicate that oral aspirin challenge induces epigenetic changes in ILFs, specifically in AERD patients, possibly via changes in TF binding, which may have epigenetic effects on the development of AERD. © Mary Ann Liebert, Inc.
DOI
10.1089/dna.2023.0218
Appears in Collections:
의과대학 > 의학과 > Journal papers
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