Genome-wide DNA methylation analysis in ankylosing spondylitis identifies HLA-B*27 dependent and independent DNA methylation changes in whole blood.
J Autoimmun
; 102: 126-132, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31128893
ABSTRACT
BACKGROUND AND OBJECTIVE:
Ankylosing spondylitis is a chronic inflammatory disease characterized by inflammation of the sacroiliac joints and the spine that can lead to significant pain, immobility, and disability. The etiology and pathogenesis of ankylosing spondylitis are incompletely understood, though most patients carry the HLA-B*27 allele. The objective of this study was to evaluate DNA methylation changes in ankylosing spondylitis with the goal of revealing novel mechanistic insights into this disease.METHODS:
Genome-wide DNA methylation analysis was performed in whole blood DNA samples using the Infinium MethylationEPIC array in patients with ankylosing spondylitis compared to age, sex, and race matched patients with osteoarthritis as a non-inflammatory disease control. We studied 24 patients with ankylosing spondylitis, including 12 patients who carry HLA-B*27 and 12 patients who are HLA-B*27 negative. DNA methylation analysis was performed with adjustment for blood cell composition in each sample.RESULTS:
We identified a total of 67 differentially methylated sites between ankylosing spondylitis patients and osteoarthritis controls. Hypermethylated genes found included GTPase-related genes, while hypomethylated genes included HCP5, which encodes a lncRNA within the MHC region, previously associated with genetic risk for psoriasis and toxic epidermal necrolysis. Carrying HLA-B*27 was associated with robust hypomethylation of HCP5, tubulin folding cofactor A (TBCA) and phospholipase D Family Member 6 (PLD6) in ankylosing spondylitis patients. Hypomethylation within HCP5 involves a CpG site that contains a single nucleotide polymorphism in linkage disequilibrium with HLA-B*27 and that controls DNA methylation at this locus in an allele-specific manner.CONCLUSIONS:
A genome-wide DNA methylation analysis in ankylosing spondylitis identified DNA methylation patterns that could provide potential novel insights into this disease. Our findings suggest that HLA-B*27 might play a role in ankylosing spondylitis in part through inducing epigenetic dysregulation.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espondilite Anquilosante
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Antígeno HLA-B27
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Metilação de DNA
Tipo de estudo:
Prognostic_studies
Limite:
Humans
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Male
Idioma:
En
Revista:
J Autoimmun
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos