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Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis
BACKGROUND: Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS. METHODS: In this st...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526246/ https://www.ncbi.nlm.nih.gov/pubmed/28743287 http://dx.doi.org/10.1186/s13075-017-1382-1 |
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author | Hao, Jiangcan Liu, Yang Xu, Jiawen Wang, Wenyu Wen, Yan He, Awen Fan, Qianrui Guo, Xiong Zhang, Feng |
author_facet | Hao, Jiangcan Liu, Yang Xu, Jiawen Wang, Wenyu Wen, Yan He, Awen Fan, Qianrui Guo, Xiong Zhang, Feng |
author_sort | Hao, Jiangcan |
collection | PubMed |
description | BACKGROUND: Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS. METHODS: In this study, we compared the genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) between five AS patients and five healthy subjects, using the Illumina Infinium HumanMethylation450 BeadChip. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the relevance of the identified differentially methylated genes for AS, using another independent sample of five AS patients and five healthy subjects. RESULTS: Compared with healthy controls, we detected 1915 differentially methylated CpG sites mapped to 1214 genes. The HLA-DQB1 gene achieved the most significant signal (cg14323910, adjusted P = 1.84 × 10(–6), β difference = 0.5634) for AS. Additionally, the CpG site cg04777551 of HLA-DQB1 presented a suggestive association with AS (adjusted P = 1.46 × 10(–3), β difference = 0.3594). qRT-PCR observed that the mRNA expression level of HLA-DQB1 in AS PBMCs was significantly lower than that in healthy control PBMCs (ratio = 0.48 ± 0.10, P < 0.001). Gene Ontology (GO) and KEGG pathway enrichment analysis of differentially methylated genes identified four GO terms and 10 pathways for AS, functionally related to antigen dynamics and function. CONCLUSIONS: Our results demonstrated the altered DNA methylation profile of AS and implicated HLA-DQB1 in the development of AS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-017-1382-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5526246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-55262462017-08-02 Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis Hao, Jiangcan Liu, Yang Xu, Jiawen Wang, Wenyu Wen, Yan He, Awen Fan, Qianrui Guo, Xiong Zhang, Feng Arthritis Res Ther Research Article BACKGROUND: Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS. METHODS: In this study, we compared the genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) between five AS patients and five healthy subjects, using the Illumina Infinium HumanMethylation450 BeadChip. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the relevance of the identified differentially methylated genes for AS, using another independent sample of five AS patients and five healthy subjects. RESULTS: Compared with healthy controls, we detected 1915 differentially methylated CpG sites mapped to 1214 genes. The HLA-DQB1 gene achieved the most significant signal (cg14323910, adjusted P = 1.84 × 10(–6), β difference = 0.5634) for AS. Additionally, the CpG site cg04777551 of HLA-DQB1 presented a suggestive association with AS (adjusted P = 1.46 × 10(–3), β difference = 0.3594). qRT-PCR observed that the mRNA expression level of HLA-DQB1 in AS PBMCs was significantly lower than that in healthy control PBMCs (ratio = 0.48 ± 0.10, P < 0.001). Gene Ontology (GO) and KEGG pathway enrichment analysis of differentially methylated genes identified four GO terms and 10 pathways for AS, functionally related to antigen dynamics and function. CONCLUSIONS: Our results demonstrated the altered DNA methylation profile of AS and implicated HLA-DQB1 in the development of AS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-017-1382-1) contains supplementary material, which is available to authorized users. BioMed Central 2017-07-25 2017 /pmc/articles/PMC5526246/ /pubmed/28743287 http://dx.doi.org/10.1186/s13075-017-1382-1 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Hao, Jiangcan Liu, Yang Xu, Jiawen Wang, Wenyu Wen, Yan He, Awen Fan, Qianrui Guo, Xiong Zhang, Feng Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis |
title | Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis |
title_full | Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis |
title_fullStr | Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis |
title_full_unstemmed | Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis |
title_short | Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis |
title_sort | genome-wide dna methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526246/ https://www.ncbi.nlm.nih.gov/pubmed/28743287 http://dx.doi.org/10.1186/s13075-017-1382-1 |
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