Epigenome-wide association study identifies Behçet’s disease-associated methylation loci in Han Chinese

Rheumatology ◽  
2019 ◽  
Vol 58 (9) ◽  
pp. 1574-1584 ◽  
Author(s):  
Hongsong Yu ◽  
Liping Du ◽  
Shenglan Yi ◽  
Qingfeng Wang ◽  
Yunyun Zhu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Association Study ◽  
Mrna Expression ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Han Chinese ◽  
Healthy Controls ◽  
Behcet's Disease ◽  
Cpg Sites ◽  
Aberrant Dna Methylation

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.

scholarly journals Glucocorticoid sensitivity in Behçet's disease

2012 ◽  
Vol 1 (2) ◽  
pp. 103-111 ◽  
Author(s):  
R A M Quax ◽  
J A M van Laar ◽  
R van Heerebeek ◽  
K Greiner ◽  
E Ben-Chetrit ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Behçet’S Disease ◽  
Gene Polymorphisms ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Healthy Controls ◽  
Behcet's Disease ◽  
Expression Levels ◽  
Mrna Expression Levels

ObjectiveGlucocorticoid (GC) sensitivity is highly variable among individuals and has been associated with susceptibility to develop (auto-)inflammatory disorders. The purpose of the study was to assess GC sensitivity in Behçet's disease (BD) by studying the distribution of four GC receptor (GR) gene polymorphisms and by measuring in vitro cellular GC sensitivity.MethodsHealthy controls and patients with BD in three independent cohorts were genotyped for four functional GR gene polymorphisms. To gain insight into functional differences in in vitro GC sensitivity, 19 patients with BD were studied using two bioassays and a whole-cell dexamethasone-binding assay. Finally, mRNA expression levels of GR splice variants (GR-α and GR-β) were measured.ResultsHealthy controls and BD patients in the three separate cohorts had similar distributions of the four GR polymorphisms. The Bcll and 9β minor alleles frequency differed significantly between Caucasians and Mideast and Turkish individuals.At the functional level, a decreased in vitro cellular GC sensitivity was observed. GR number in peripheral blood mononuclear cells was higher in BD compared with controls. The ratio of GR-α/GR-β mRNA expression levels was significantly lower in BD.ConclusionsPolymorphisms in the GR gene are not associated with susceptibility to BD. However, in vitro cellular GC sensitivity is decreased in BD, possibly mediated by a relative higher expression of the dominant negative GR-β splice variant. This decreased in vitro GC sensitivity might play an as yet unidentified role in the pathophysiology of BD.

Quality of life and diet: A paired match study on Behçet’s disease

2022 ◽  
pp. 1-11
Author(s):  
Murat Urhan ◽  
Reci Meseri ◽  
Fahrettin Oksel
Keyword(s):  
Quality Of Life ◽  
Behçet’S Disease ◽  
Diet Quality ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Short Form ◽  
Activity Levels ◽  
Healthy Controls ◽  
Behcet's Disease

BACKGROUND: It has been reported that the quality of life and diet quality in individuals with rheumatological diseases are poor and may adversely affect the course of the disease. OBJECTIVE: This study aims to compare the quality of life and diet of individuals with Behçet’s Disease (BD) compared to healthy controls. METHODS: This study was planned as a case-control study, and 60 adult patients with BD were compared with age (±1) and sex paired match healthy controls concerning the quality of life and diet. Diet quality was assessed using nutrient adequacy ratio (NAR) and the mean adequacy ratio (MAR) values calculated from 24 h dietary food recall and obesity was also evaluated by various anthropometric measurements. The Short Form-36 Health Survey (SF-36) was used to evaluate the quality of life (QoL). In addition, the 24-hour physical activities were recorded to calculate physical activity levels (PAL). Data were analyzed by SPSS 25.0 via paired sample t-test and McNemar (and McNemar-Bowkers) test. p <  0.05 was deemed significant. RESULTS: The findings showed that cases were more obese (p = 0.005), less physically active (p <  0.001), had lower QoL (p <  0.01 for all subscales) and had higher Beck depression scores (p = 0.001). Controls had higher means of energy (p <  0.001), CHO% (p = 0.025), fat% (p = 0.004), and fiber (p = 0.007) intake and mean MAR value (p <  0.001). CONCLUSIONS: Compared to healthy controls, patients with BD were more obese, had lower QoL and lower diet quality. Therefore, people with BD should be evaluated for comorbid diseases and be supported by health professionals, such as dietitians and psychologists.

Association ofERAP1Gene Polymorphisms With Behçet's Disease in Han Chinese

2015 ◽  
Vol 56 (10) ◽  
pp. 6029 ◽  
Author(s):  
Lijun Zhang ◽  
Hongsong Yu ◽  
Minming Zheng ◽  
Hua Li ◽  
Yunjia Liu ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Han Chinese ◽  
Behcet's Disease

Hypermethylation of IL‐10 gene is responsible for its low mRNA expression in Behçet's disease

2018 ◽  
Vol 119 (8) ◽  
pp. 6614-6622 ◽  
Author(s):  
Shahriar Alipour ◽  
Mohammad Nouri ◽  
Alireza Khabbazi ◽  
Nasser Samadi ◽  
Zohreh Babaloo ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Behcet's Disease

scholarly journals Leukocyte toll-like receptor expression in pathergy positive and negative Behçet’s disease patients

Rheumatology ◽  
2020 ◽  
Vol 59 (12) ◽  
pp. 3971-3979
Author(s):  
Tim B van der Houwen ◽  
Willem A Dik ◽  
Marco Goeijenbier ◽  
Manizhah Hayat ◽  
Nicole M A Nagtzaam ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Receptor Expression ◽  
Healthy Controls ◽  
Toll Like Receptor ◽  
Behcet's Disease ◽  
Tnf Α ◽  
Classical Monocytes

Abstract Objectives To investigate whether the auto-inflammatory nature and the pathergic reaction in Behçet’s disease (BD) are driven by a disturbed toll-like receptor (TLR) response. Methods We compared both TLR expression by flow-cytometry and TLR response by stimulation assay in 18 BD patients (both pathergy positive and pathergy negative) with 15 healthy controls. Results Expression of TLR1 and 2 was significantly elevated in B-lymphocytes of BD patients compared with healthy controls. TLR1, 2 and 4 were significantly more highly expressed in both CD4+ and CD8+ T-lymphocytes of BD patients. Granulocytes of BD patients displayed significantly higher expression of TLR1, 2, 4 and 6. TLR2, 4 and 5 expression was significantly increased on classical monocytes of BD patients. Intermediate monocytes of BD patients showed an increase in expression of TLR2. Furthermore, TLR2 and 5 were significantly more highly expressed in non-classical monocytes of BD patients. In pathergy positive patients, TLR5 was even more highly expressed compared with pathergy negative patients on B- and T-lymphocytes and granulocytes. Furthermore, TLR2 and 5 showed an elevated TNF-α response to stimulation with their cognate ligands. Conclusion Immune cells of BD patients overexpress TLR1, 2, 4, 5 and 6. Furthermore, after stimulation of TLR2 and 5, BD patients demonstrate a more potent TNF-α response. Although this is a small cohort, in the pathergy positive patients, TLR5 expression is even further augmented, suggesting that a microbial (flagellin) or damage (HMGB1) associated signal may trigger the exaggerated immune response that is characteristic for the pathergy phenomenon in BD. In conclusion, these results point to an exaggerated TLR response in the auto-inflammatory nature of BD.

scholarly journals Association of a TNIP1 Polymorphism with Vogt-Koyanagi-Harada Syndrome but Not with Ocular Behcet’s Disease in Han Chinese

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e95573 ◽  
Author(s):  
Yanyun Shi ◽  
Yading Jia ◽  
Shengping Hou ◽  
Jing Fang ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Han Chinese ◽  
Behcet's Disease
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