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Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis. | LitMetric

Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis.

Arthritis Res Ther

Key Laboratory of Trace Elements and Endemc Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, People's Republic of China.

Published: July 2017

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, 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, 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526246PMC
http://dx.doi.org/10.1186/s13075-017-1382-1DOI Listing

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