Abstract

Behçet's disease (BD) is a chronic inflammatory vasculitis affecting multiple organs. Uveitis is frequently seen in patients with BD, especially in Turkish population. To investigate vascular endothelial growth factor (VEGF) gene polymorphisms along with the levels of VEGF and VEGF receptors in patients with Behçet's uveitis (BU). Fifty-five BD-associated uveitis patients and 30 ageand sex-matched controls were included in this case-control study. The genotypes of the single nucleotide poymorphisms (SNPs): rs2010963 (+405G), rs3025039 (+936T) and rs699947 (-2598A) of the VEGF-A gene were determined using real-time polymerase chain reaction (RT-PCR) and serum levels of VEGF and VEGF receptors were measured using enzyme-linked immunosorbent assay (ELISA). No associations of the VEGF gene polymorphisms were observed in BD uveitis patients, but arthritis was present in 53.3% of patients not possessing CT genotype in C3025039→T polymorphism (p = 0.024). Although there were no statistically significant differences in serum VEGF-A, VEGF-C and soluble vascular endothelial growth factor receptor-3 (sVEGFR-3) levels (p < 0.05), serum vascular endothelial growth factor receptor-1 (VEGFR-1) and sVEGFR-3 levels were significantly higher in the BD group (p < 0.001 and p = 0.001, respectively). In addition, VEGF-C/soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) ratio was significantly higher (p < 0.001), while VEGF-A/VEGFR-1 and VEGF-C/sVEGFR-3 ratios were significantly lower (p < 0.001 and p = 0.033, respectively) in BD patients compared to controls. Also, VEGF-C/sVEGFR-3 (p = 0.024, r = 0.37) and VEGF-C/sVEGFR-2 (p = 0.020, r = 0.38) ratios were positively correlated with disease duration. The significant changes in sVEGFR-3 levels and VEGF-C/sVEGFR-3 ratio has shown that lymphangiogenesis processes might take place in the pathogenesis of BD uveitis, and these parameters can be important indicators of evaluation of BD patients with uveitis together with disease duration.

Highlights

  • Behçet’s disease (BD) is a chronic inflammatory vasculitis affecting multiple organs

  • No associations of the vascular endothelial growth factor (VEGF) gene polymorphisms were observed in BD uveitis patients, but arthritis was present in 53.3% of patients not possessing CT genotype in C3025039→T polymorphism (p = 0.024)

  • There were no statistically significant differences in serum VEGF-A, VEGF-C and soluble vascular endothelial growth factor receptor-3 levels (p < 0.05), serum vascular endothelial growth factor receptor-1 (VEGFR-1) and sVEGFR-3 levels were significantly higher in the BD group (p < 0.001 and p = 0.001, respectively)

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Summary

Introduction

Behçet’s disease (BD) is a chronic inflammatory vasculitis affecting multiple organs. Behçet’s disease (BD) was described by Turkish dermatologist Dr Hulusi Behçet as a disease with triple symptoms: oral aphthae, genital ulcers and uveitis with hypopyon.[1] Behçet’s disease is a systemic immuno-inflammatory vasculitis occurring in young adults that is characterized by endothelial cell dysfunction. Ocular involvement can be the first finding in most BD patients from 2 to 4 years after disease onset, and it is one of the most important causes of morbidity as it may result in blindness.[2,3] It is more frequent and more severe in Turkish and Japanese BD patients. In a study conducted in Turkey, eye involvement in form of uveitis/retinal vasculitis was reported in 29.1% of patients, while early age of onset and male gender were poor prognostic factors for ocular findings.[4,5]

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