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Objective: Behçet's disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behçet's disease in a diverse multiethnic population. Methods: A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray‐24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. Results: We identified 2 novel genetic susceptibility loci for Behçet's disease, including a risk locus in IFNGR1 (rs4896243) (odds ratio [OR] 1.25; P = 2.42 × 10−9) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 × 10−8). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide‐stimulated monocytes. In addition, our results replicated the association (P < 5 × 10−8) of 6 previously identified susceptibility loci in Behçet's disease: IL10, IL23R, IL12A‐AS1, CCR3, ADO, and LACC1, reinforcing the notion that these loci are strong genetic factors in Behçet's disease shared across ancestries. We also identified >30 genetic susceptibility loci with a suggestive level of association (P < 5 × 10−5), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behçet's disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated. Conclusion: We performed the largest genetic association study in Behçet's disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries. [ABSTRACT FROM AUTHOR]

Behçet's disease is an inflammatory disease characterized by recurrent oral and genital ulcers and significant organ involvement. Localizing the genetic association between HLA-B*51 and Behçet's disease and exploring additional susceptibility loci in the human leukocyte antigen (HLA) region are complicated by the strong linkage disequilibrium in this region. We genotyped 8,572 variants in the extended HLA locus and carried out imputation and meta-analysis of 24,834 variants in 2 independent Behçet's disease cohorts from 2 ancestry groups. Genotyped SNPs were used to infer classical HLA alleles in the HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1 and HLA-DRB1 loci. Our data suggest that the robust HLA-B*51 association in Behçet's disease is explained by a variant located between the HLA-B and MICA genes (rs116799036: odds ratio (OR) = 3.88, P = 9.42 × 10−50). Three additional independent genetic associations within PSORS1C1 (rs12525170: OR = 3.01, P = 3.01 × 10−26), upstream of HLA-F-AS1 (rs114854070: OR = 1.95, P = 7.84 × 10−14) and with HLA-Cw*1602 (OR = 5.38, P = 6.07 × 10−18) were also identified and replicated. [ABSTRACT FROM AUTHOR]

Aim: To determine serum lipid, lipoproteins and oxidized low density lipoprotein (oxLDL) levels in Behçet's disease (BD) and to evaluate the relationship of these parameters with the clinical activity of the disease. Materials and Methods: Sixty-two patients (25 active, 37 inactive) and --26 healthy controls were included in the study. We measured serum oxLDL levels using the enzyme-linked immunosorbent assay method, and serum total cholesterol (TC), triglyceride (TG) and high density lipoprotein-cholesterol (HDL-C) levels by spectrophotometric method. Results: Serum TG (108±70 mg/dL and 79±40 mg/dL, respectively; P<0.05), LDL-C (124±35 mg/ dL and 108±26 mg/dL, respectively; P<0.05) and oxLDL (65±19 U/L and 53±10 U/L, respectively; P<0.01) levels were significantly higher in patients than in controls, but HDL-C levels were significantly lower in patients than in controls (39±11 mg/dL and 50±13 mg/dL, respectively; P<0.05). The levels of oxLDL in patients were found to correlate with those of TC and LDL-C. Neither the lipid parameters nor the oxLDL levels in the patients with active disease (n=25) were different than those in the patients who were in inactive stage (n=37). Serum levels of oxLDL in the patients with active and inactive disease were significantly higher than those in controls (66±19 U/L, 65±19 U/L, and 53±10 U/L, respectively; P<0.05). Conclusions: We conclude that the increase of TG, LDL-C and oxLDL levels and the decrease of HDL-levels may indicate that there is a tendency to atherothrombotic process in patients with BD. Inflammation and immunologic reactions in BD may be caused by a response to elevated oxLDL. TG, LDL-C and oxLDL are not useful markers for the severity of the disease activity. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effects of short-term chlorambucil therapy in the management of uveitis due to Behcet's disease.Methods: Forty-four patients with refractory uveitis associated with Behcet's disease who had had short-term chlorambucil therapy for about 23 weeks were included in the study. The frequency of attacks (number of attacks per year) and the longest period between the attacks were analyzed to evaluate the efficiency of the therapy. The therapy was judged to be effective if the patient had < or =1 attack a year and/or > or =1 year between the attacks.Results: The mean follow-up time was 51.4 +/- 32.5 months (range: 13-122 months). Following the therapy, the mean frequency of attacks had decreased from 4.9 +/- 2.3 to 0.9 +/- 1.4 (p < 0.0001) and the mean longest period between the attacks was prolonged from 4.4 +/- 2.3 months to 25.7 +/- 23.1 months (p < 0.0001). The ratio of severe attacks had decreased from 74.1 +/- 34% to 51.3 +/- 36.6% (p = 0.0218). The best-corrected visual acuity was increased in 32.9%, decreased in 34.2%, and the same in 32.9% of the eyes. Phytsis bulbi developed in three (3.8%) eyes. New attacks were seen in 56.8% of patients and another immunosuppressive agent(s) was given to 40.9% of the patients 1-8 months after treatment. No serious side effects were observed during the chlorambucil therapy.Conclusion: Short-term chlorambucil therapy for refractory uveitis in Behcet's disease is effective in controlling the disease in two-thirds of patients. [ABSTRACT FROM AUTHOR]

Behçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease. A total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients. Genetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B / MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10−8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B / MICA (rs116799036, OR = 1.45, P = 1.95 × 10−8), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10−7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. Male patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease. • Male patients with Behçet's disease have a higher disease genetic risk. • Genetic risk within the HLA class I region was higher in male compared to female patients with Behçet's disease. • Sex-specific genetic bias might influence disease presentation in Behçet's disease. [ABSTRACT FROM AUTHOR]