SNP-mediated binding of TBX1 to the enhancer element of IL-10 reduces the risk of Behcet’s disease

Epigenomics ◽  
2021 ◽  
Author(s):  
Handan Tan ◽  
Guannan Su ◽  
Xiao Tan ◽  
Yang Qin ◽  
Lin Chen ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Mobility Shift ◽  
Enhancer Activity ◽  
Enhancer Element ◽  
Behcet's Disease ◽  
Increased Risk

Aims: The genetic association between Behcet’s disease susceptibility and IL-10 has been confirmed in multiple cohorts, but the underlying mechanism of this association remains unclear. Materials & methods: We combined public resources and laboratory experiments (electrophoretic mobility shift assays, chromatin immunoprecipitation, luciferase reporter gene and CRISPR/Cas9 genome editing) to analyze transcription factor binding and enhancer activity controlling IL-10 expression. Results & conclusion: The T allele of noncoding rs3024490 within super-enhancer elements is able to specifically bind TBX1 and, in turn, promotes the enhancer activity and increased expression of IL-10. However, a relative deficiency in TBX1 in Behcet’s disease patients leads to the low expression of IL-10 and increased risk of developing Behcet’s disease.

Behcet’s disease and pregnancy: obstetrical and neonatal outcomes in a population-based cohort of 12 million births

2019 ◽  
Vol 47 (4) ◽  
pp. 381-387 ◽  
Author(s):  
Seohyuk Lee ◽  
Nicholas Czuzoj-Shulman ◽  
Haim Arie Abenhaim
Keyword(s):  
Venous Thromboembolism ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
The United States ◽  
Population Based ◽  
Fetal Outcomes ◽  
Behcet's Disease ◽  
Increased Risk ◽  
In Pregnancy

AbstractBackgroundBehcet’s disease (BD) is a rare, multi-systemic inflammatory disorder for which only limited and contradictory data exists in the context of pregnancy. Our objective was to estimate the prevalence of BD in pregnancy and to evaluate maternal and fetal outcomes associated with pregnant women living with BD.MethodsUsing the 1999–2013 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from the United States, we performed a population-based retrospective cohort study consisting of pregnancies that occurred during this time period. ICD-9 codes were used to identify delivery admissions to women with or without BD. Multivariate logistic regression was used to estimate the adjusted effects of BD on maternal and fetal outcomes.ResultsAmong the 12,592,676 pregnancies in our cohort, 144 were to women with BD, for an overall prevalence of 1.14 cases/100,000 births between 1999 and 2013. Over the study period, the prevalence of BD rose from 0.5 to 2.4/100,000 births. Women with BD demonstrated a two-fold greater frequency of non-delivery hospital admissions during pregnancy, and were more likely to be Caucasian, have private medical insurance, be of the upper income quartiles, and deliver at an urban teaching hospital. Women with BD were at greater risk for preterm labor and postpartum venous thromboembolism, while their newborns were more likely to be born premature.ConclusionBD-associated pregnancies are increasing in prevalence and are associated with a greater risk for adverse maternal and fetal outcomes in pregnancy. Appropriate thromboprophylaxis during pregnancy should be considered given the increased risk for venous thromboembolism.

Common FMF alleles may predispose to development of Behcet's disease with increased risk for venous thrombosis

2007 ◽  
Vol 36 (1) ◽  
pp. 48-52 ◽  
Author(s):  
E. Rabinovich ◽  
Y. Shinar ◽  
M. Leiba ◽  
M. Ehrenfeld ◽  
P. Langevitz ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Behcet's Disease ◽  
Increased Risk

Pediatric Behçet’s Disease and Thromboses

2010 ◽  
Vol 38 (2) ◽  
pp. 387-390 ◽  
Author(s):  
BRICE KRUPA ◽  
ROLANDO CIMAZ ◽  
SEZA OZEN ◽  
MICHEL FISCHBACH ◽  
PIERRE COCHAT ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
International Study ◽  
Retrospective Chart Review ◽  
Lower Limbs ◽  
Disease Course ◽  
Protein C Deficiency ◽  
Behcet's Disease ◽  
Increased Risk

Objective.To describe the characteristics of a group of pediatric patients with Behçet’s disease (BD) who presented at least 1 episode of thrombosis during their disease course.Methods.We made a retrospective chart review of the clinical, biological, and radiological data of children with BD who presented at least 1 episode of either arterial or venous thrombosis. Data were extracted from both an international pediatric Behçet cohort and files referred from 7 French centers.Results.Twenty-one patients were included. Diagnosis of BD was based on the criteria of the International Study Group for BD. Main locations for thrombosis were the cerebral sinuses, in 11 patients (52.4%); and lower limbs, in 9 patients (40.9%). Recurrent episodes were observed in 4 patients (21%). Thrombophilia measurements were normal in 14 patients out of 21, while anticardiolipin antibodies were positive in 4 patients, and 2 out of 21 had protein C deficiency. One patient had lupus anticoagulant. All patients were treated with colchicine. Corticosteroids were also added for variable periods in 13 patients. Five patients out of 21 were treated with anticoagulants (heparin, then anti-vitamin K) and 3 with antiplatelets (acetylsalicylic acid).Conclusion.Thromboses are a serious complication of BD and may occur early in the disease course. The presence of thrombophilic markers could increase the risk of thrombosis in BD, but the size of our population does not allow any conclusion. An international cohort (PED-BD) is currently in place and will allow study of such cases longitudinally, as well as assessment of the elements that correlate with an increased risk of thrombosis in children with BD.

scholarly journals A putative functional variant within the UBAC2 gene is associated with increased risk of Behçet's disease

2011 ◽  
Vol 63 (11) ◽  
pp. 3607-3612 ◽  
Author(s):  
Amr H. Sawalha ◽  
Travis Hughes ◽  
Ajay Nadig ◽  
Vuslat Yılmaz ◽  
Kenan Aksu ◽  
...  
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Behcet's Disease ◽  
Increased Risk ◽  
Functional Variant

scholarly journals Pharmacotherapy for Behçet’s Disease and the Risk of Malignancy

2021 ◽  
Vol 12 ◽  
Author(s):  
Mao-Xin Huang ◽  
Cai-Yun Wang ◽  
Jin-Yan Guo ◽  
Jian-Hao Li ◽  
Xiao-Hong Li ◽  
...  
Keyword(s):  
High Risk ◽  
Protective Factors ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Control Group ◽  
Behcet's Disease ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
The Relationship

Background: Behçet’s disease (BD) is associated with an increased risk of cancer. Few reports have been published on the relationship between drug exposure and the risk of cancer in patients with BD. Herein, we explored the relationship between pharmacologic interventions for BD and the risk of cancer.Methods: we carried out a retrospective nested case-control study in a cohort of BD patients from attending our institution. Among 1,148 patients, 22 cancer patients were individually 1:2 matched to 44 cancer-free controls. The following biochemical indicators were evaluated: routine blood analysis, liver and kidney function tests, inflammatory indexes, blood gas analysis, blood electrolyte and previous pharmacologic interventions to manage BD including systemic glucocorticoids, methotrexate, cyclosporine-A, azathioprine, cyclophosphamide (CYC), and thalidomide, which are considered the primary medicines used for the management of BD.Results: Among the 22 BD patients with cancers, myelodysplastic syndrome (MDS) (22.72%) was the most common type. Furthermore, CYC administration was significantly higher in BD patients with cancer compared with the cancer-free matched control group. Further, we observed that complement 4 (C4) (odds ratio [OR] = 0.0001, 95% confidence interval [CI]: 0.001–0.065) and hemoglobin (Hb) (OR = 0.891, 95% CI: 0.795–0.998) levels were independent protective factors for predicting cancer risk in BD patients on multivariate analyses.Conclusion: Our study revealed that CYC was associated with a high risk of cancer in BD patients. Furthermore, C4 and Hb are independent protective factors for oncogenesis in BD patients. These findings may provide references and suggestions for clinicians to select appropriate treatments and for the early recognition of high-risk patients to reduce cancer incidence in BD patients.

scholarly journals The relation of PON1-L55M gene polymorphism and clinical manifestation of Behcet's disease.

2014 ◽  
Vol 61 (2) ◽  
Author(s):  
Ahmet Dursun ◽  
Salih Cicek ◽  
Fatih M Keni ◽  
Sevim Karakas-Celik ◽  
Tuna Sezer ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Gene Polymorphism ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Clinical Manifestations ◽  
Control Group ◽  
Free Oxygen Radicals ◽  
Behcet's Disease ◽  
Increased Risk

Behçet's disease is a multisystem disease characterized by recurrent oral and genital ulcers, relapsing uveitis, mucocutaneous, articular, gastrointestinal, neurologic, and vascular manifestations. Paraoxonase is believed to play an important role in protection of LDL and HDL particles from oxidation, in antioxidant effect against lipid peroxidation on cellular membranes, and in anti-inflammatory process. Lipid peroxidation and free oxygen radicals have been thought to play a role in pathogenesis of BD. The association of paraoxonase gene polymorphisms with Behçet's Disease in a group of Turkish patients with clinical manifestations and healthy controls has been investigated. Paraoxonase (PON-1-L55M) gene polymorphism was investigated in 50 Behcet patients and 50 healthy individuals with a PCR/RFLP method. There were significant differences between patients and the control group in allele frequencies of the PON1 L55M polymorphism (p=0.04). Also, when patients were compared with the control group according to clinical manifestations, this statistical significance was getting sharper. Compared with the PON55 L allele, the M allele was associated with greater than 3.5 fold (OR 3.5, 95% CI 1.3-8.9) increased risk of ocular (OR 2.4, 95% CI 1.1-5.3), 2.4 fold joint and 3.1 fold (OR 3.1, 95% CI 1.1-8.4) central nervous system manifestations of BD. The PON L55M gene polymorphism seemed to play a role in the pathogenesis of BD.

Cancer incidence in Behçet's Disease.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13583-e13583
Author(s):  
Deniz Can Guven ◽  
Ertugrul Cagri Bolek ◽  
Sabri Engin Altintop ◽  
Burcu Celikten ◽  
Burak Yasin Aktas ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Behçet’S Disease ◽  
Cancer Incidence ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Incidence Rates ◽  
Behcet's Disease ◽  
Increased Risk ◽  
And Gender ◽  
Risk Of Cancer

e13583 Background: Previous studies demonstrated increased risk of cancer in systemic autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus (SLE) and sjögren syndrome due to uncontrolled inflammation. Behçet’s disease (BD) was also reported to be associated with an increased risk of cancer, although data is limited and differences in study designs was an important issue. In this study, we aimed to assess cancer incidence in a large cohort of BD patients and to compare with the data of the Turkish National Cancer Registry (TNCR) in the same age and gender groups. Methods: The study cohort consisted of BD patients of > 18 years old age and without a prior cancer diagnosis who were prospectively recorded in Hacettepe University Vasculitis Center. Data on any cancer was collected from the patient files. Cancer incidence was compared with age- and gender-specific cancer incidence rates of the normal population retrieved from the 2014 Turkish National Cancer Registry (TNCR) data using standardized incidence rates (SIR). Results: Totally 451 adult cases with BD were included in the study. The median age of the cohort was 43 (20-75) and 52.5% of the patients were males. Eleven cancer cases were observed during a median 124 months follow up. Behçet’s Disease was associated with an increase in cancer risk compared to expected counts in the corresponding age and sex group (SIR 2.84, 95% CI 1.50-4.94, p < 0.001). Cancer risk was particularly increased in men (SIR: 5.63, 95% CI: 2.62–10.70, p < 0.001) compared to TNCR data. Patients with papulopustular lesions had a trend towards a decreased risk of cancer (p = 0.060) and patients using azathioprine had a significantly decreased cancer risk (p = 0.031). Conclusions: This study revealed the cancer risk of patients BD was increased approximately three times compared to corresponding age and sex group. Besides the routine care, increased attention for cancer surveillance is required in the follow-up of BD patients.

Sign in / Sign up

Export Citation Format

Share Document