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Epigenome-wide association study identifies Behçet's disease-associated methylation loci in Han Chinese.
- Source :
-
Rheumatology . Sep2019, Vol. 58 Issue 9, p1574-1584. 11p. 1 Color Photograph, 1 Chart, 3 Graphs, 1 Map. - Publication Year :
- 2019
-
Abstract
- Objective The aetiology of Behçet's disease (BD), known as a systemic vasculitis, is not completely understood. Increasing evidence suggests that aberrant DNA methylation may contribute to the pathogenesis of BD. The aim of this epigenome-wide association study was to identify BD-associated methylation loci in Han Chinese. Methods Genome-wide DNA methylation profiles were compared between 60 BD patients and 60 healthy controls using the Infinium Human Methylation 450 K Beadchip. BD-associated methylation loci were validated in 100 BD patients and 100 healthy controls by pyrosequencing. Gene expression and cytokine production was quantified by real-time PCR and ELISA. Results A total of 4332 differentially methylated CpG sites were associated with BD. Five differentially methylated CpG sites (cg03546163, cg25114611, cg20228731, cg23261343 and cg14290576) revealed a significant hypomethylation status across four different genes (FKBP5 , FLJ43663 , RUNX2 and NFIL3) and were validated by pyrosequencing. Validation results showed that the most significant locus was located in the 5'UTR of FKBP5 (cg03546163, P = 3.81E-13). Four CpG sites with an aberrant methylation status, including cg03546163, cg25114611, cg23261343 and cg14290576, may serve as a diagnostic marker for BD (area under the receiver operating curve curve = 83.95%, 95% CI 78.20, 89.70%). A significantly inverse correlation was found between the degree of methylation at cg03546163 as well as cg25114611 and FKBP5 mRNA expression. Treatment with a demethylation agent, 5-Aza-2'-deoxycytidine resulted in an increase of FKBP5 mRNA expression and a stimulated IL-1β production. Conclusion Our findings suggest that aberrant DNA methylation, independently of previously known genetic variants, plays a vital role in the pathogenesis of BD. Trial registration Chinese Clinical Trial Registry, chictr.org.cn, ChiCTR-CCC-12002184. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DEOXYCYTIDINE
*BEHCET'S disease
*CONFIDENCE intervals
*CYTOKINES
*ENZYME-linked immunosorbent assay
*GENETIC polymorphisms
*INTERLEUKINS
*MESSENGER RNA
*NURSING models
*POLYMERASE chain reaction
*RISK assessment
*RECEIVER operating characteristic curves
*DNA methylation
*DEMETHYLATION
*GENE expression profiling
*SEQUENCE analysis
*EPIGENOMICS
*DISEASE risk factors
*EVALUATION
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 14620324
- Volume :
- 58
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Rheumatology
- Publication Type :
- Academic Journal
- Accession number :
- 138251669
- Full Text :
- https://doi.org/10.1093/rheumatology/kez043