Vitamin D receptor gene polymorphisms in Iranian Azary patients with Behçet's disease.

OBJECTIVES: The aim of our study was to investigate the association of four polymorphisms of the VDR gene (FokI, BsmI, TaqI, and ApaI) with their susceptibility to Behçet's disease (BD) and their clinical manifestations with respect to the Iranian Azari population. METHOD: In this cross-sectional study we considered the BsmI, FokI, ApaI, and TaqI polymorphisms in 50 Iranian Azary patients with BD and 50 healthy controls, with the use of polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). RESULTS: A significant difference was found for the FokI polymorphism between the case and control groups. The f allele frequency of 26% was present in BD patients, compared to only 13% in the control group. In addition, the f/f genotype was significantly associated with BD. We found no significant differences between the BD and control groups regarding the distribution of ApaI, BsmI, and TaqI genotype frequencies. We found no association between VDR polymorphisms and the clinical manifestations of BD. CONCLUSIONS: The VDR f allele and f/f genotype are associated with BD in the Iranian Azari population.

Lack of association of TNFAIP3 and JAK1 with Behçet's disease in the European population.

OBJECTIVES: Behçet's disease (BD) is an immune-mediated and complex disease which has been associated with HLA class I molecules although other genes such as IL23R and IL10 have also been involved in the susceptibility to BD. Recently, an association of variants of the JAK1 and TNFAIP3 genes with the disease has been reported in the Chinese Han population. The aim of the present work was to asses whether the association described in Asian populations is replicated in Europeans. METHODS: This study includes a total of 1155 Spanish subjects of European origin (372 BD and 783 unrelated healthy individuals). Patients were recruited from different hospitals and controls were collected in the same geographic regions and they matched with patients in age and gender. A total of five SNPs, two in the JAK1 gene: rs2780815 and rs310241 and the other three in the TNFAIP3: rs10499194, rs9494885 and rs610604, were included in this study. The genotyping of these SNPs was performed using a real time PCR system (TaqMan® SNP Genotyping Assays). RESULTS: No statistically significant differences were found when the patient and control groups were compared. The distribution of the risk alleles was similar in patients with and without eye manifestations and in patients with and without HLA-B*51. CONCLUSIONS: The association of variants of the genes JAK1 and the TNFAIP3 with BD which has been described in the Chinese population was not replicated in Europeans.

Associations between major histocompatibility complex class I chain-related gene A polymorphisms and susceptibility to Behcet's disease. A meta-analysis.

OBJECTIVE: The purpose of this work was to investigate whether major histocompatibility complex class I chain-related gene A (MICA) polymorphisms are associated with susceptibility to Behcet's disease (BD). METHODS: A meta-analysis was conducted on the associations between the MICA-transmembrane (TM) A6 allele and the 009 allele of MICA exon 2-4 (MICA*009) and BD with or without HLA-B51 overall and in each ethnic group. RESULTS: Fifteen comparison studies were included in this meta-analysis. The meta-analysis revealed a significant association between the MICA-TM A6 allele and BD in European, Asian, and Arab populations [odds ratio (OR) 1.436, 95 % confidence interval (CI) 1.111-1.857, p = 0.006; OR 1.999, 95 % CI 1.551-2.575, p = 8.0 × 10(-8); OR 1.333, 95 % CI 1.058-2.300, p = 0.025, respectively,]). Stratification by HLA-B51 showed an association between the MICA-TM A6 allele and BD with HLA-B51 in the overall group and in the European population. Meta-analysis showed a significant association between the MICA*009 allele and BD in the overall group (OR 3.948, 95 % CI 2.680-5.815, p < 1.0 × 10(-8)) and in the European population (OR 3.392, 95 % CI 2.118-5.433, p = 5.6 × 10(-6)). A significant association was found between the MICA*009 allele and B51-positive BD. CONCLUSION: This meta-analysis shows that the MICA-TM A6 allele and the MICA*009 allele are associated with BD susceptibility in various ethnic populations, and that MICA alleles are in strong linkage disequilibrium with HLA-B51 in BD.

Single nucleotide polymorphisms in IL-10-mediated signalling pathways in Korean patients with Behçet's disease.

OBJECTIVES: Previous genome-wide association studies have demonstrated an association between the IL-10 region and Behçet's disease (BD) in Turkish and Japanese populations. Our aim was to fully examine the relationship between IL-10 and BD, the associations between BD and single nucleotide polymorphisms (SNPs) in IL-10-mediated signalling pathways (JAK1, TYK2, and STAT3) were examined in Korean patients with BD. METHODS: DNA samples were obtained from 223 patients who met the international study group criteria for BD and from 222 age- and sex-matched healthy controls. Twenty-four tag SNPs in JAK1, STAT3, and TYK2 were selected for genotyping based on the Japanese panel of international HapMap data with a minor allele frequency >5% and r2 >0.8. RESULTS: The allele-based analysis showed that the T allele of rs310245 in JAK1 was associated with BD (odds ratio [95% confidence interval] = 1.34 [1.03-1.76], p=0.031), which lost statistical significance after permutation-based correction for multiple testing. In the genotype-based analysis, the JAK1 rs310245 TT homozygote (1.79 [1.14-2.82], p=0.012) and the STAT3 rs2293152 GG homozygote (2.01 [1.16-3.47], p=0.011) showed associations with BD. However, these associations did not achieve significance after correction for multiple testing. We did not observe any genetic interaction between the JAK1 rs310245 TT homozygote and the STAT3 rs2293152 GG homozygote. In the haplotype analysis, GT haplotype at rs17127024 and rs310245 (1.34 [1.03-1.74], p=0.032), and the AA haplotype at rs2256298 and rs3818753 (1.41 [1.03-1.92], p=0.034) in JAK1 were associated with BD, but lost statistical significance after correction for multiple testing. CONCLUSIONS: There was no significant association between BD and SNPs in IL-10-mediated intracellular signalling in Korean patients.

PTPN2 rs1893217 single-nucleotide polymorphism is associated with risk of Behçet's disease in a Chinese Han population.

OBJECTIVES: Behçet's disease (BD) is a rare, chronic, relapsing, systemic, immune-mediated vasculitis and the etiology remains to be defined. This study investigated single-nucleotide polymorphisms (SNP) of tyrosine-protein phosphatase non-receptor type 2 (PTPN2) and inducible T-cell co-stimulator-ligand gene (ICOSLG) in Chinese Han BD patients and healthy controls because SNPs of these two genes are associated with risk of developing other auto-inflammation diseases. METHODS: A total of 407 BD patients and 679 ethnically matched healthy controls were recruited for genotyping of PTPN2 rs1893217, rs2542151, rs2847297 and rs7234029 SNPs and ICOSLG rs2838519 and rs762421 SNPs using a Sequenom MassArray system. RESULTS: PTPN2 rs1893217 was associated with risk of developing BD (χ2=10.01, pc=0.040), while the PTPN2 rs2542151 genotype had a weak association in basic genotype analysis (χ2=7.49, p=0.024), but it could not withstand the strongest Bonferroni correction (pc=0.14). In contrast, PTPN2 rs2847297 and rs7234029 and ICOSLG rs2838519 and rs762421 did not correlate with BD risk. Moreover, logistic analysis with the additive, dominant and recessive genetic models did not reveal any statistical difference between BD cases and controls (pc>0.05). In addition, associations were observed between the two SNPs (rs1893217, rs2542151) and the patients with gastrointestinal involvement (pc=0.027, pc=0.032, respectively). CONCLUSIONS: PTPN2 variant rs1893217 was associated with risk of BD development in a Han Chinese population. Further study will confirm this finding and investigate the role of PTPN2 in development of BD.

Registry of the Spanish network of Behçet's disease: a descriptive analysis of 496 patients.

OBJECTIVES: To describe the clinical features of a large cohort of 496 Spanish patients with Behçet's disease (BD) and to analyse if patient's sex influenced the initial and cumulated prevalence of disease manifestations. METHODS: Retrospective and descriptive study of 496 patients recruited in sixteen centres on the frame of the Spanish Registry of Behçet Disease Project Group. Demographic and clinical data are presented in addition to treatments and their related adverse effects. Clinical features at disease onset and during follow-up were compared according to the sex of the patients. RESULTS: On the whole series, female to male ratio was 1.2:1.0. Mean age at disease onset was 28.7±12.6 years (range 17-73). Oral ulcers were the most frequent initial manifestation presented in 52.0% of patients. During follow-up, eye inflammatory disease was recorded in 45.1% of patients; thrombosis in 19.7% and central nervous system involvement in 13.5%. Men had higher prevalence of ocular involvement and venous thrombosis (52.5% vs. 39.2%, p=0.004 and 26.3% vs. 9.6%, p<0.001, respectively). CONCLUSIONS: Spanish patients with BD presented similar clinical characteristics as their counterpart in the same geographical area and other world regions. In addition, we confirmed that ocular and vascular involvements are more frequent in men than in women.

Genetic variant on PDGFRL associated with Behçet disease in Chinese Han populations.

Behçet disease is a complex multisystem disorder. This study aimed to explore the predisposition of PDGFRL at the 8p21.3 locus with Behçet disease and its expression level for different genotypes. A two-stage association study was performed in 719 patients and 1,820 controls for 26 tagSNPs in the PDGFRL gene. Real-time PCR and Bonferroni correction were performed. The first-stage study showed that SNP rs17633132 was associated with Behçet disease (Pc = 5.20 × 10(-3)). Replication and combined studies showed consistent association for rs17633132 T allele and TT genotype (replication: Pc = 3.90 × 10(-4) and 5.70 × 10(-3); combined: Pc = 2.05 × 10(-6) and 3.20 × 10(-4)). No haplotype in PDGFRL was associated with Behçet disease. The expression of PDGFRL in skin from rs17633132 CC genotype individuals was increased compared to that in those with the CT or TT genotype (P = 0.028, P = 0.032, respectively). This study identified a Behçet-disease-associated gene, PDGFRL, and suggests its involvement of Behçet disease by modulating its transcription.

Multisystemic diseases and ethnicity: a focus on lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease.

We present an overview of the association between ethnicity and the clinical and epidemiological aspects of four multisystemic diseases: lupus erythematosus, systemic sclerosis, sarcoidosis and Behçet disease. In particular, we highlight observed ethnic differences in cutaneous manifestations of these diseases. This article should help guide clinical management, as well as serve to highlight future areas for research.

Patient-driven assessment of disease activity in Behçet's syndrome: cross-cultural adaptation, reliability and validity of the Turkish version of the Behçet's Syndrome Activity Score.

OBJECTIVES: The Behçet's Syndrome Activity Score (BSAS) is the first patient reported outcome measure developed to assess the global disease activity in patients with Behçet's syndrome (BS). We aimed to evaluate the reliability and validity of the Turkish version of BSAS for measuring disease activity in BS. We further investigated the performance of Routine Assessment of Patient Index Data (RAPID)3, a patient-reported index originally developed for rheumatoid arthritis, in BS patients. METHODS: Patients seen consecutively at a tertiary Rheumatology Centre were requested to complete BSAS and multidimensional health assessment questionnaire (MDHAQ). Besides, all attending physicians filled the Behçet's Disease Current Activity Form (BDCAF). Descriptive statistics and Pearson correlation coefficients were calculated accordingly for the reliability and validity assessments of BSAS. RESULTS: A total of 104 patients completed all three assessments. The test-retest reliability of BSAS has a good level (ICC=0.84, 95% CI [0.69-0.94]). The mean scores for BSAS, BDCAF and RAPID3 were 39±20.8, 3.2±1.4 and 9.2±5.6, respectively. BSAS was correlated with BDCAF moderately (r=0.587), while it was moderately correlated with RAPID3 (r=0.648). The correlation between the RAPID3 and BDCAF was moderate (r=0.403), but lower as compared to the correlations between the other instruments. CONCLUSIONS: We found that the BSAS has modest correlation with BDCAF and is a reliable and valid patient reported measure of disease activity that can be used to assess patients with BS. An outcome score composed of only patient-derived observations may have the additional advantage of being easier to use in a routine care setting. Demonstration of a moderate level of correlation between RAPID3 and BDCAF (close to the level of weak relationship), suggests that RAPID3 likely needs more investigations before recommending its use in BS.

TIR-domain-containing adaptor protein gene TIRAP S180L polymorphism is not increased in Behçet's disease patients in two ethnic cohorts.

OBJECTIVES: The single nucleotide polymorphism (SNP) of TIRAP (Serine 180 leucine, S180L) that is shown to be associated with Behçet's disease (BD) in a European-derived cohort, but not in Middle Eastern patients is investigated in two other populations. METHODS: Two cohorts of BD patients and controls from Turkey (n=797) and Italy (n=633) were genotyped by sequence specific primer-polymerase chain reaction (SSP-PCR) or TaqMan q-PCR assays. RESULTS: Genotype and allele frequencies in TIRAP S180L (rs8177374) were not different between BD patients and controls in either ethnicity. Furthermore, a meta-analysis between the Turkish and the Italian BD cohorts did not reveal an association between this non-synonymous SNP in TIRAP and BD (meta-analysis OR=0.94, meta-analysis p=0.61, Q statistic heterogeneity p=0.11). CONCLUSIONS: TIRAP S180L gene polymorphism, which was previously shown to be associated with BD in a Caucasian population, has been replicated in either Turkish or Italian population in our study.

Association study of IL10 and IL23R-IL12RB2 in Iranian patients with Behçet's disease.

OBJECTIVE: Independent replication of the findings from genome-wide association studies (GWAS) remains the gold standard for results validation. Our aim was to test the association of Behçet's disease (BD) with the interleukin-10 gene (IL10) and the IL-23 receptor-IL-12 receptor ß2 (IL23R-IL12RB2) locus, each of which has been previously identified as a risk factor for BD in 2 different GWAS. METHODS: Six haplotype-tagging single-nucleotide polymorphisms (SNPs) in IL10 and 42 in IL23R-IL12RB2 were genotyped in 973 Iranian patients with BD and 637 non-BD controls. Population stratification was assessed using a panel of 86 ancestry-informative markers. RESULTS: Subtle evidence of population stratification was found in our data set. In IL10, rs1518111 was nominally associated with BD before and after adjustment for population stratification (odds ratio [OR] for T allele 1.20, 95% confidence interval [95% CI] 1.02-1.40, unadjusted P [P(unadj) ] = 2.53 × 10(-2) ; adjusted P [P(adj) ] = 1.43 × 10(-2) ), and rs1554286 demonstrated a trend toward association (P(unadj) = 6.14 × 10(-2) ; P(adj) = 3.21 × 10(-2) ). Six SNPs in IL23R-IL12RB2 were found to be associated with BD after Bonferroni correction for multiple testing, the most significant of which were rs17375018 (OR for G allele 1.51, 95% CI 1.27-1.78, P(unadj) = 1.93 × 10(-6) ), rs7517847 (OR for T allele 1.48, 95% CI 1.26-1.74, P(unadj) = 1.23 × 10(-6) ), and rs924080 (OR for T allele 1.29, 95% CI 1.20-1.39, P = 1.78 × 10(-5) ). SNPs rs10489629, rs1343151, and rs1495965 were also significantly associated with BD in all tests performed. Results of meta-analyses of our data combined with data from other populations further confirmed the role of rs1518111, rs17375018, rs7517847, and rs924080 in the risk of BD, but no epistatic interactions between IL10 and IL23R-IL12RB2 were detected. Results of imputation analysis highlighted the importance of IL23R regulatory regions in the susceptibility to BD. CONCLUSION: These findings independently confirm, extend, and refine the association of BD with IL10 and IL23R-IL12RB2. These associations warrant further validation and investigation in patients with BD, as they may have implications for the development of novel therapies (e.g., immunosuppressive therapy targeted at IL-23p19).

Identification of a susceptibility locus in STAT4 for Behçet's disease in Han Chinese in a genome-wide association study.

OBJECTIVE: To identify susceptibility loci for Behçet's disease (BD) and elucidate their functional role. METHODS: A genome-wide association study (GWAS) and functional studies were conducted. A total of 149 patients and 951 controls were enrolled in the initial GWAS, and 554 patients and 1,159 controls were enrolled in the replication study. Real-time polymerase chain reaction, luciferase reporter assay, and enzyme-linked immunosorbent assay were performed. RESULTS: Our GWAS and replication studies identified a susceptibility locus around STAT4 (single-nucleotide polymorphisms [SNPs] rs7574070, rs7572482, and rs897200; P = 3.36 × 10(-7) to 6.20 × 10(-9) ). Increased expression of STAT4 was observed in individuals carrying the rs897200 risk genotype AA. Consistent with the idea that STAT4 regulates the production of interleukin-17 (IL-17) and interferon-γ, IL17 messenger RNA and protein levels were increased in individuals carrying the rs897200 risk genotype AA. Interestingly, the risk allele A of rs897200 creates a putative transcription factor binding site. To test whether it directly affects STAT4 transcription, an in vitro luciferase reporter gene assay was performed. Higher transcription activity was observed in individuals carrying the risk allele A, suggesting that rs897200 is likely to directly affect STAT4 expression. Additionally, 2 SNPs, rs7574070 and rs7572482, which are tightly linked with rs897200, were cis-expression quantitative trait loci (eQTL) SNPs, suggesting that SNP rs897200 is an eQTL SNP. Most importantly, the clinical disease severity score was higher in individuals with the rs897200 risk genotype AA. CONCLUSION: These findings strongly suggest that STAT4 is a novel locus underlying BD. We propose a model in which up-regulation of STAT4 expression and subsequent STAT4-driven production of inflammatory cytokines, such as IL-17, constitute a potential pathway leading to BD.

[Behçet's disease: clinical and demographic associations].

AIM: To comparatively study the clinical manifestations, sexual and HLA-B51 associations in patients with Behçet's disease (BD) in two ethnic groups. SUBJECTS AND METHODS: The authors examined 143 patients with the valid diagnosis of BED who were divided into 2 groups: 1) 85 patients, the dwellers of Dagestan (a multiethnic cohort), 63 men and 22 women (mean age 29 +/- 7.4 years); 2) 58 Russian men and women (mean age 33 +/- 11.7 years). RESULTS: Two major criteria for BD, such as aphthous stomatitis and external genital ulcers, were found with the same frequency. Panuveitis and angiitis of the retina were diagnosed more frequently in the Dagestani population with BD than in the Russians. Out of the minor criteria for BD, the incidence of lower limb deep venous thrombosis was 23% for the Dagestanis versus 3% for the Russians. Arterial thromboses and pulmonary artery aneurysms became causes of death in 4 in 5 men aged 19-23 years from their Dagestani ancestry. HLA B51 (B marker) was found in the dwellers of Dagestan: in 70% of the men and 40% of the women who had BD. CONCLUSION: BD runs a more severe course in male patients and is characterized by severe eye diseases and the systematic pattern of the process at young age. Gender-specific and genetic aspects call for further comparative investigations on large ethnic patient cohorts of other ancestries.

CC chemokine receptor 5 polymorphism in Italian patients with Behcet's disease.

OBJECTIVE: To evaluate the potential role of CC chemokine receptor 5 (CCR5)Δ32 polymorphism in the susceptibility to and clinical expression of Behçet's disease (BD) in a cohort of Italian patients. METHODS: One hundred and ninety-six consecutive Italian patients satisfying the ISG criteria for BD were followed up for 8 years, and 180 healthy age- and sex-matched blood donors were molecularly genotyped for the CCR5Δ32 polymorphism. A standard microlymphocytotoxicity technique was used to serotype HLA-B51. The patients were subgrouped on the basis of the presence or absence of clinical manifestations. RESULTS: The distribution of the CCR5Δ32 genotype differed between BD patients and controls (P = 0.02). The CCR5Δ32 allele was more common in BD patients than in controls [P = 0.02, odds ratio (OR) 2.28 (95% CI 1.1, 4.8)]. Carriers of the CCR5Δ32 allele (Δ32/Δ32 + CCR5/Δ32) were significantly more common in BD patients than in controls [P = 0.02, OR 2.37 (95% CI 1.1, 5.1)]. Population-attributable risk was 7.1%. In categorizing patients according to gender, the association between CCR5Δ32 polymorphism and BD was similar in females and males (ORs 2.76 and 2.0, respectively). No significant differences were found when the frequencies of clinical manifestations were compared between CC5RΔ32 allele carriers and non-carriers. CONCLUSION: CCR5Δ32 polymorphism is associated with an increased susceptibility to develop BD. Chemokines may have a role in the pathophysiology of BD.

Replication of a microsatellite genome-wide association study of Behcet's disease in a Korean population.

OBJECTIVE: Behçet's disease is one of the major aetiologies of uveitis causing blindness in Asian countries. A genome-wide association study identified six microsatellite markers as disease susceptibility loci for Japanese patients with Behçet's disease. To confirm our recent results, these microsatellite markers were examined in a Korean population as a replication study. METHODS: Study participants included 119 Behçet's disease patients and 141 controls. All were enrolled in Korea. Association between the six reported microsatellite markers (D3S0186i, D6S0014i, D6S0032i, 536G12A, D12S0645i and D22S0104i) and Behçet's disease was analysed. HLA-B was genotyped by sequence-based typing methods. RESULTS: A microsatellite marker located near the HLA-B region demonstrated significant association with Behçet's disease (P = 0.028). The genotype and phenotype frequencies of the HLA-B*51 gene were significantly increased in patients (23.1 and 39.5%, respectively) compared with healthy controls (11.2 and 20.1%, respectively; P < 0.001). CONCLUSION: Microsatellite analysis revealed that the HLA-B*51 gene was strongly associated with Behçet's disease in a Korean population.

Behçet's syndrome: a critical digest of the recent literature.

A similar disease severity among men and women in Brasil, a high frequency of gastrointestinal involvement in China, Japan and USA, a low frequency of pathergy positivity in Japan and USA underline the ethnic variations reported in recent studies. Polymorphisms pertaining both to innate and adaptive immunity in genome wide association studies, clusters in phenotype, and new mechanisms for emerging therapeutic implications have been reported. A Th17 dominance seems to be likely with the exception of gastrointestinal involvement. Infliximab, interferon-alpha and cyclosporine-A may be showing their beneficial effects also by affecting the Th17 cells. The clinical course and outcome of isolated pulmonary artery thrombosis is similar to pulmonary artery aneurysms. Parenchymal lesions (nodules, consolidations, cavities and ground glass lesions) are common in patients with pulmonary involvement. Pericarditis is a frequent cardiac manifestation in France. Treatment of BS became more intensive than before. Immunosuppressives and corticosteroids seem to prevent relapses of venous thrombosis. Studies are needed to understand the role of anticoagulants. Interferon alpha-2a appears to be effective at lower dosage, which brings the advantage of decreased cost and increased tolerability. Switching between anti-TNF agents, when needed, is possible. Interleukin-1 and interleukin-6 are new promising targets.

SUMO4 C438T polymorphism is associated with papulopustular skin lesion in Korean patients with Behçet's disease.

Small ubiquitin-like modifier 4 (SUMO4) is involved in a range of autoimmune diseases and is known to downregulate the transcription activity of nuclear factor kappa B (NF-κB). Our objective was to investigate the association of a certain polymorphism (C438T) of the SUMO4 gene with Behçet's disease (BD) in terms of its incidence and clinical features in Korean patients. We consecutively enrolled 83 patients with BD and 120 healthy controls. Genomic DNA was extracted from whole-blood samples. We identified a single nucleotide change (C438T) in the SUMO4 gene using an amplification refractory mutation system (ARMS) technique. To validate the ARMS technique, we compared its results to the results of direct sequencing in 20 subjects. HLA-B51 status was determined by polymerase chain reaction sequence-specific primers. The presence of papulopustular lesions (P = 0.006) and vascular involvement (P = 0.045) was significantly different between C438T genotypes in HLA-B51-positive patients with BD. There were no differences in allelic or genotypic frequencies of the SUMO4 C438T polymorphism between patients with BD and controls (P = 0.567 and P = 0.818, respectively). The difference in papulopustular skin lesions between CC and CT + TT genotypes in HLA-B51-positive patients with BD was also statistically significant (P = 0.002, OR = 23.40, 95% CI: 2.33-235.54). The C438T polymorphism in the SUMO4 gene is associated with significantly increased risk of papulopustular skin lesions in HLA-B51-positive patients.

MEFV, TNFRSF1A and CARD15 mutation analysis in Behçet's disease.

OBJECTIVES: Given the pathological similarities between Behçet's disease (BD), Familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS) and Crohn's disease (CD) we evaluated the frequency of mutations and polymorphisms in MEFV, TNFRSF1A and CARD15 in Israeli BD patients of either Jewish or Arab descent. METHODS: Fifty-four BD patients (11 Jews and 43 Arabs), evaluated with respect to the entire spectrum of BD disease manifestations, were granted a systemic severity score for BD. An association between BD manifestations and MEFV, TNFRSF1A and CARD15 variants was analysed. RESULTS: Twelve patients (20.7%) displayed a single MEFV mutation and four patients (7.4%) had two mutated FMF alleles. Two patients (3.8%) carried a CARD15 variation and none carried a TNFRSF1A polymorphism. The frequency and distribution of mutated alleles between patients and controls was comparable (p=0.27). No statistically significant differences between carriers and non-carriers with respect to disease manifestations and severity score were calculated. Arab patients were diagnosed earlier than Jewish patients (25.8±11.6 and 37.2±10.7, respectively, p=0.06). CONCLUSIONS: The overall MEFV high carrier frequency in our cohort of BD patients seems to be attributed to their Mediterranean extraction rather than related to BD. The propensity of Arab patients (79.6%) in a cohort of BD patients from northern Israel is highlighted in face of their proportion (20%) in the general population lending further support to arguments that favour a genetic component for BD.

Association of a CARD9 Gene Haplotype with Behcet's Disease in a Chinese Han Population.

Purpose: To investigate the association of CARD9 gene polymorphisms with Behcet's disease (BD) and acute anterior uveitis (AAU) in a Chinese Han population.Methods: We performed a case-control association study in 480 patients with BD, 1151 patients with AAU and 1440 healthy controls. Six single nucleotide polymorphisms (SNPs) of CARD9 were genotyped, including rs4077515, rs11145769, rs59902911, rs9411205, rs4073153 and rs1135314.Results: None of the individual SNPs in the CARD9 gene showed an association with either BD or AAU. Haplotype analysis revealed a significant decrease of the frequency of a CARD9 gene haplotype CGCCA (rs4077515, rs11145769, rs59902911, rs9411205, rs4073153) in BD when compared to healthy controls (Pc = 0.012, OR = 0.585, 95%CI = 0.409 ~ 0.837). Haplotype analysis did not show an association between CARD9 and AAU.Conclusions: This study shows that a five-SNP haplotype of the CARD9 gene (CGCCA) may be a protective factor for BD with ocular involvement, but not for AAU.

Prevalence and clinical features of systemic diseases in Chinese patients with uveitis.

PURPOSE: Systemic diseases are frequently associated with uveitis but are often not recognised by clinicians. An estimate of the prevalence in a large-scale uveitis population is essential for understanding the epidemiological profile and may be helpful for clinical practice. DESIGN: A nationwide survey. METHODS: Data were obtained from a national database which included the registration of uveitis cases from 23 provinces, 5 autonomous regions and 4 municipalities across mainland China. The primary outcome was identification of a systemic disease associated with uveitis. RESULTS: From April 2008 through August 2018, 15 373 uveitis patients were included in the study. Males accounted for 52.9%, and the mean (SD) age of uveitis onset was 35.4 (15.9) years. After standardisation for age, the prevalence of systemic disease among patients with uveitis was 30.8% (95% CI, 30.1% to 31.6%). Vogt-Koyanagi-Harada disease (VKH; age-standardised prevalence, 12.7%; 95% CI, 12.1% to 13.2%), Behçet's disease (BD; 8.7%; 95% CI, 8.3% to 9.2%), ankylosing spondylitis (AS; 5.0%; 95% CI, 4.6% to 5.3%) and juvenile idiopathic arthritis (JIA; 1.2%; 95% CI, 1.0% to 1.3%) were the most common entities among 36 different forms of systemic diseases identified. The prevalence was significantly higher in males (37.0%; 95% CI, 36.0% to 38.1%) than in females (23.6%; 95% CI, 22.6% to 24.6%), and also higher in bilateral uveitis patients (41.2%; 95% CI, 40.2% to 42.2%) compared with unilateral cases (14.3%; 95% CI, 13.4% to 15.2%), and was highest in panuveitis (59.5%; 95% CI, 58.2% to 60.8%). CONCLUSION: Approximately one third of uveitis patients in this nationwide survey have an associated systemic disease, whereby VKH, BD, AS and JIA are the most frequent entities seen in China.