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Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria
BACKGROUND: Chronic spontaneous urticaria (CSU) is a common autoimmune skin disease. Little is known about the role of epigenetics in the pathogenesis of CSU. This study aimed to investigate genome-wide DNA methylation profile in whole blood of patients with CSU. PATIENTS AND METHODS: Genome-wide DN...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448194/ https://www.ncbi.nlm.nih.gov/pubmed/34539625 http://dx.doi.org/10.3389/fimmu.2021.681714 |
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author | Qi, Yumeng Zhang, Liming Yang, Xiaonan Tang, Biao Xiao, Ting |
author_facet | Qi, Yumeng Zhang, Liming Yang, Xiaonan Tang, Biao Xiao, Ting |
author_sort | Qi, Yumeng |
collection | PubMed |
description | BACKGROUND: Chronic spontaneous urticaria (CSU) is a common autoimmune skin disease. Little is known about the role of epigenetics in the pathogenesis of CSU. This study aimed to investigate genome-wide DNA methylation profile in whole blood of patients with CSU. PATIENTS AND METHODS: Genome-wide DNA methylation levels in whole blood samples of 95 Chinese Han ethnicity adult CSU patients and 95 ethnicity-, age- and sex-matched healthy controls were analyzed using Illumina 850K methylation chip. The differentially methylated genes (DMGs) were screened out and then functionally annotated by the gene ontology and the Kyoto encyclopedia of genes and genomes databases. RESULTS: A total of 439 differentially methylated positions (DMPs) (p < 0.01 and |Δβ| ≥ 0.06) were identified with 380 hypomethylated and 59 hypermethylated. The average global DNA methylation levels of the 439 DMPs in the CSU patients were significantly lower than those in the healthy controls (p < 0.001). The distribution of the 439 DMPs was wide on chromosome 1 to 22 and chromosome X. Chromosome 6 embodied the largest number of DMPs (n = 51) and their annotated genes were predominantly related to autoimmunity. The 304 annotated DMGs were mainly enriched in autoimmune disease- and immune-related pathways. A total of 41 DMPs annotated to 28 DMGs were identified when p < 0.01 and |Δβ| ≥ 0.1. Of the 28 DMGs, HLA-DPB2, HLA-DRB1, PPP2R5C, and LTF were associated with autoimmunity. CSU cases with elevated total IgE, positive anti-thyroid peroxidase IgG autoantibodies, positive anti-thyroglobulin IgG autoantibodies, angioedema, UASday > 4, or recurrent CSU showed phenotype-specific DMPs as compared with cases with normal total IgE, negative anti-thyroid peroxidase IgG autoantibodies, negative anti-thyroglobulin IgG autoantibodies, no angioedema, UASday ≤ 4, or non-recurrent CSU respectively. CONCLUSION: This study shows a distinct genome-wide DNA methylation profile in Chinese Han ethnicity adult CSU patients and indicates a role of epigenetics in the pathogenesis of CSU. The predominant enrichment of the CSU-associated DMGs in immunological pathways provides supportive evidence for the immunopathogenesis of CSU. Future research on the CSU-associated DMPs and DMGs will help discover potential therapeutic targets for CSU. |
format | Online Article Text |
id | pubmed-8448194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84481942021-09-18 Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria Qi, Yumeng Zhang, Liming Yang, Xiaonan Tang, Biao Xiao, Ting Front Immunol Immunology BACKGROUND: Chronic spontaneous urticaria (CSU) is a common autoimmune skin disease. Little is known about the role of epigenetics in the pathogenesis of CSU. This study aimed to investigate genome-wide DNA methylation profile in whole blood of patients with CSU. PATIENTS AND METHODS: Genome-wide DNA methylation levels in whole blood samples of 95 Chinese Han ethnicity adult CSU patients and 95 ethnicity-, age- and sex-matched healthy controls were analyzed using Illumina 850K methylation chip. The differentially methylated genes (DMGs) were screened out and then functionally annotated by the gene ontology and the Kyoto encyclopedia of genes and genomes databases. RESULTS: A total of 439 differentially methylated positions (DMPs) (p < 0.01 and |Δβ| ≥ 0.06) were identified with 380 hypomethylated and 59 hypermethylated. The average global DNA methylation levels of the 439 DMPs in the CSU patients were significantly lower than those in the healthy controls (p < 0.001). The distribution of the 439 DMPs was wide on chromosome 1 to 22 and chromosome X. Chromosome 6 embodied the largest number of DMPs (n = 51) and their annotated genes were predominantly related to autoimmunity. The 304 annotated DMGs were mainly enriched in autoimmune disease- and immune-related pathways. A total of 41 DMPs annotated to 28 DMGs were identified when p < 0.01 and |Δβ| ≥ 0.1. Of the 28 DMGs, HLA-DPB2, HLA-DRB1, PPP2R5C, and LTF were associated with autoimmunity. CSU cases with elevated total IgE, positive anti-thyroid peroxidase IgG autoantibodies, positive anti-thyroglobulin IgG autoantibodies, angioedema, UASday > 4, or recurrent CSU showed phenotype-specific DMPs as compared with cases with normal total IgE, negative anti-thyroid peroxidase IgG autoantibodies, negative anti-thyroglobulin IgG autoantibodies, no angioedema, UASday ≤ 4, or non-recurrent CSU respectively. CONCLUSION: This study shows a distinct genome-wide DNA methylation profile in Chinese Han ethnicity adult CSU patients and indicates a role of epigenetics in the pathogenesis of CSU. The predominant enrichment of the CSU-associated DMGs in immunological pathways provides supportive evidence for the immunopathogenesis of CSU. Future research on the CSU-associated DMPs and DMGs will help discover potential therapeutic targets for CSU. Frontiers Media S.A. 2021-09-03 /pmc/articles/PMC8448194/ /pubmed/34539625 http://dx.doi.org/10.3389/fimmu.2021.681714 Text en Copyright © 2021 Qi, Zhang, Yang, Tang and Xiao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Qi, Yumeng Zhang, Liming Yang, Xiaonan Tang, Biao Xiao, Ting Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria |
title | Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria |
title_full | Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria |
title_fullStr | Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria |
title_full_unstemmed | Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria |
title_short | Genome-Wide DNA Methylation Profile in Whole Blood of Patients With Chronic Spontaneous Urticaria |
title_sort | genome-wide dna methylation profile in whole blood of patients with chronic spontaneous urticaria |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448194/ https://www.ncbi.nlm.nih.gov/pubmed/34539625 http://dx.doi.org/10.3389/fimmu.2021.681714 |
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