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.

Cancer incidence in Behçet's disease.

BACKGROUND: Previous studies demonstrated an increased cancer risk in autoimmune diseases. Behçet's disease (BD) was also reported to be associated with an increased risk of cancer, although the data is limited. AIMS: In this study, we aimed to assess cancer incidence in a large cohort of BD patients and to compare with the data of the same age and gender groups. METHODS: The study cohort consisted of BD patients of > 18 years of age who were prospectively recorded in the 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. 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 of 124 months follow-up. Behçet's disease was associated with an increase in cancer risk compared with expected counts in the corresponding age and sex group (SIR 2.84, 95% CI 1.50-4.94, p < 0.001). Patients with papulopustular lesions had a trend toward a decreased risk of cancer (p = 0.060), and patients using azathioprine had a significantly decreased cancer risk (p = 0.031). CONCLUSION: This study revealed BD patients had approximately three times increased cancer risk compared with corresponding age and sex groups. Besides the routine care, increased attention for cancer surveillance is required in the follow-up of BD patients.

Meta-analysis of associations between interleukin-10 polymorphisms and susceptibility to Behcet's disease.

The aim of this study was to determine whether interleukin-10 (IL-10) polymorphisms are associated with susceptibility to Behcet's disease (BD). A meta-analysis was conducted, examining the associations between the IL-10 - 1082 G/A, - 819 C/T, and - 592 C/A polymorphisms and BD in various ethnic groups. Fourteen studies involving 5992 patients and 8966 controls were considered in the meta-analysis. Meta-analysis of the IL-10 - 1082 G/A polymorphism showed no association between BD and the - 1082 G allele (odds ratio (OR) = 0.951, 95% confidence interval (CI) = 0.790-1.146, p = 0.601). Meta-analysis of the IL-10 - 819 C/T polymorphism revealed a significant association between BD and the - 819 C allele (OR = 0.751, 95% CI = 0.684-0.825, p < 0.001) in all study subjects. Stratification by ethnicity indicated a significant association between the - 819 C allele and BD in Turkish (OR = 0.779, 95% CI = 0.709-0.856, p < 0.001) and Asian (OR = 0.676, 95% CI = 0.631-0.725, p < 0.001), but not in Middle Eastern populations. Meta-analysis of the - 592 C allele showed an association with BD in all study subjects (OR = 0.792, 95% CI = 0.662-0.948, p = 0.011) Stratification by ethnicity indicated a significant association between the - 592 C allele and BD in Asian populations (OR = 0.656, 95% CI = 0.512-0.841, p = 0.001). This meta-analysis showed that the IL-10 - 819 C/T and - 592 C/A polymorphisms are associated with BD susceptibility, especially in Asian population.

Association of LACC1, CEBPB-PTPN1, RIPK2 and ADO-EGR2 with ocular Behcet's disease in a Chinese Han population.

BACKGROUND: An Immunochip study recently identified the association of a number of new genetic loci with Behcet's disease (BD). OBJECTIVE: To confirm the association between new genetic loci reported in an Immunochip study and BD in a Han Chinese population. METHODS: A two-stage association study was carried out in 1238 patients with BD and 1458 healthy controls. Twenty-two candidate single nucleotide polymorphisms (SNPs) were selected for genotyping by iPLEXGold genotyping or TaqMan SNP assays and a meta-analysis was performed for significantly associated markers. RESULTS: The results showed that four SNPs (LACC1/rs9316059, CEBPB-PTPN1/rs913678, ADO-EGR2/rs224127 and RIPK2/rs10094579) were associated with BD in an allelic association test (rs9316059 T allele: pc=4.95×10-8, OR=0.687; rs913678 C allele: pc=3.01×10-4, OR=1.297; rs224127 A allele: pc=3.77×10-4, OR=1.274; rs10094579 A allele: pc=6.93×10-4, OR=1.302). For four SNPs tested by meta-analysis, the association with BD was strengthened and all exceeded genome-wide significance (rs9316059: p=2.96×10-16; rs913678: p=2.09×10-16; rs224127: p=5.28×10-13; rs10094579: p=9.21×10-11). CONCLUSIONS: Our findings confirmed the association of four loci (LACC1, CEBPB-PTPN1, ADO-EGR2 and RIPK2) in Chinese Han patients with BD.

The Association of Chemokine Gene Polymorphisms with VKH and Behcet's Disease in a Chinese Han Population.

To investigate the association of chemokine gene polymorphisms and Behcet's disease (BD) and Vogt Koyanagi Harada (VKH) disease in a Chinese Han population. A case-control study was performed. Three hundred and seventy-one BD patients, 371 VKH disease patients, and 605 healthy controls were recruited to determine genetic variants of 26 SNPs in 12 chemokine genes with iPLEX Gold genotyping assay and Sequenom MassARRAY or TaqMan SNP assays. In this study, Puncorr values showed a weak association of five SNPs of five genes in BD and three SNPs of three genes in VKH disease. However, after Bonferroni correction, the 26 investigated SNPs showed no significant differences in genetic variants, including genotype and allele frequencies, between BD or VKH disease patients and healthy individuals. Haplotype analysis for the chemokine genes showed a significant association with the TC haplotype of CXCL12 in VKH. Stratified gender analysis and genotype-phenotype analysis were conducted to analyze the association of the 26 SNPs of 12 chemokine genes with BD and VKH disease. However, no significant association was observed after Bonferroni correction. This study showed no association of 26 SNPs in 12 chemokine genes with both BD and VKH disease in a Chinese Han population.

HLA-B51 Carriers are Susceptible to Ocular Symptoms of Behçet Disease and the Association between the Two Becomes Stronger towards the East along the Silk Road: A Literature Survey.

PURPOSE: Behçet disease (BD) is predominantly found between East Asia and the Mediterranean basin along the historic Silk Road. HLA-B51 is known to be strongly associated with BD. We investigated the association between HLA-B51 and the ocular manifestations of BD among various ethnic groups. METHODS: A literature survey was conducted, and 18 articles written in English were reviewed. RESULTS: A strong correlation was found between HLA-B51 and ocular lesions in the entire cohort discussed in the reviewed articles (OR = 1.76, p = 0.000057). HLA-B51 was shown to have a strong association with ocular manifestations of BD patients in East-Eurasian (OR = 2.40, p = 0.0030) and Middle-Eurasian (OR = 1.87, p = 0.0045), but not in West-Eurasian (OR = 1.28, p = 0.35) areas. This correlation seemed to become stronger towards the east. CONCLUSIONS: A meta-analysis showed that the correlation became stronger towards the east along the Silk Road. The study results may facilitate understanding of the etiology and characteristics of BD.

Association of TNFSF4 Polymorphisms with Vogt-Koyanagi-Harada and Behcet's Disease in Han Chinese.

To investigate whether single nucleotide polymorphisms (SNPs) of the Tumor Necrosis Factor Superfamily 4 (TNFSF4) gene are associated with Vogt-Koyanagi-Harada (VKH) and Behcet's disease (BD) in a Chinese Han population. A two-stage case control study was carried out in 1331 VKH, 938 BD and 1752 healthy controls. Ten TNFSF4 SNPs, including rs1234314, rs1234315, rs2205960, rs704840, rs2795288, rs844654, rs12039904, rs10912580, rs844665, and rs844644, were genotyped using the PCR-restriction fragment length polymorphism method. Genotype and allele frequencies were analyzed between cases and healthy controls using the X2 or Fisher's exact test and p values were corrected for multiple comparisons. We observed a significantly increased frequency of the TT genotype of rs1234315 in BD patients (Pc = 1.44 × 10-5, OR = 1.734, 95% CI = 1.398-2.151). The frequency of the TT genotype of rs12039904 was significantly higher in patients with VKH disease as compared to controls (Pc = 4.62 × 10-5, OR = 1.959, 95% CI = 1.483-2.588). Analysis of clinical manifestations in VKH disease and BD did not show an association with the TNFSF4 gene polymorphisms. The study suggests that the TNFSF4 gene may be involved in the susceptibility to VKH disease and BD in Han Chinese.

Genetic polymorphisms of cell adhesion molecules in Behcet's disease in a Chinese Han population.

Cell adhesion molecules (CAMs) are involved in various immune-mediated diseases. This study was conducted to investigate the association of single nucleotide polymorphisms (SNPs) of CAMs with Behçet's disease (BD) in a Chinese Han population. A two-stage association study was carried out in 1149 BD patients and 2107 normal controls. Genotyping of 43 SNPs was performed using MassARRAY System (Sequenom), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan SNP assays. The expression of CD6 and CD11c was examined by real-time PCR and cytokine production was measured by ELISA. A significantly higher frequency of the CT genotype, and a lower frequency of the CC genotype and C allele of CD6 rs11230563 were observed in BD as compared with controls. Analysis of CD11c rs2929 showed that patients with BD had a significantly higher frequency of the GG genotype and G allele, and a lower frequency of the AG genotype as compared with controls. Functional experiments showed an increased CD11c expression and increased production of TNF-α and IL-1beta by LPS stimulated PBMCs in GG carriers of CD11c rs2929 compared to AA/AG carriers. Our study provides evidence that CD6 and CD11c are involved in the susceptibility to BD in a Chinese Han population.

Behçet's disease, hospital-based prevalence and manifestations in the Rotterdam area.

INTRODUCTION: Behçet's disease is most prevalent in countries along the former Silk Road. Prevalence varies from 70-420 per 100,000 in Turkey, and 13.5-20 and 1-2 per 100,000 in Asia and Western Europe, respectively. Additionally, disease severity and morbidity might be correlated with ethnicity. We studied demography and morbidity in the Dutch cohort of patients with Behçet's disease and compared those with known figures. PATIENTS AND METHODS: The prevalence of Behçet's patients in the Rotterdam area was determined by comparing the total number of patients within the ethnic population with the number of patients diagnosed with Behçet's disease. Patient files of the Erasmus University Medical Centre (Erasmus MC) were reviewed for morbidity figures and compared with existing data. RESULTS: In total 84 Behçet's patients of Dutch, Turkish or Moroccan descent were identified in the Rotterdam area. Prevalence of Behçet's disease differed per ethnicity: 1, 71 and 39 per 100,000 for Dutch-Caucasians, Turks, and Moroccans, respectively. These figures are comparable with occurrence in West Turkey and Morocco. Within the studied Erasmus MC cohort no significant differences in morbidity appeared between the ethnic groups. However, uveitis and pustules were significantly more common in the Erasmus MC cohort as compared with UK, German, Turkish and Moroccan cohorts. DISCUSSION AND CONCLUSIONS: We present the first epidemiological study of Behçet's disease in the Netherlands. The prevalence of Behçet's disease in the studied Dutch region and in countries of ancestry is similar. Morbidity is equally spread, compared with other countries, but uveitis and pustules seem to be more common in the Netherlands.

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.

Brief report: association of CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 With Behçet's disease in Iranians.

OBJECTIVE: To independently replicate the top findings from 4 published genome-wide association studies (GWAS) of susceptibility genes in Behçet's disease (BD). METHODS: We tested 14 single-nucleotide polymorphisms (SNPs) in 13 genomic loci (excluding the major histocompatibility complex [MHC], IL10, and IL23R-IL12RB2, which have already been associated with BD in Iranians) for allelic and genotypic associations with BD in 973 patients and 828 controls from Iran and performed meta-analyses of the significantly associated markers. RESULTS: Six SNPs (in decreasing order of significance, rs7616215 located 38 kb downstream of CCR1, rs2617170 [p.Asn104Ser] in KLRC4, rs17810546 in IL12A-AS1, rs7574070 in STAT4, and rs10050860 [p.Asp575Asn] and rs13154629 in ERAP1) were nominally associated with BD in both allelic association tests (5.05 × 10(-9) ≤ Pallele ≤ 7.55 × 10(-3) ) and sex-adjusted genotypic association tests (6.01 × 10(-9) ≤ adjusted P value ≤ 1.30 × 10(-2) ). For all 6 SNPs tested by meta-analysis (Pmeta ), the association with BD was strengthened, because the direction and magnitude of association were similar across populations (e.g., for rs7574070, odds ratio [OR] for A allele 1.29 [95% confidence interval (95% CI) 1.21-1.37], Pmeta = 2.34 × 10(-16) ; for rs7616215, OR for C allele 0.70 [95% CI 0.65-0.76], Pmeta = 1.54 × 10(-19) ; for rs17810546, OR for A allele 0.60 [95% CI 0.52-0.70], Pmeta = 6.34 × 10(-11) ; for rs2617170, OR for T allele 0.76 [95% CI 0.70-0.81], Pmeta = 2.75 × 10(-14) ; for rs13154629, OR for TT genotype 2.76 [95% CI 2.01-3.80], Pmeta = 3.57 × 10(-10) ). CONCLUSION: This study reinforces the notion that CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 are bona fide susceptibility genes for BD, in addition to the MHC, IL10, and IL23R-IL12RB2 loci. Future genetic and functional studies are now warranted to uncover the roles of these genes in the pathogenesis of BD.

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.

No association between Bach2 gene polymorphisms with Vogt-Koyanagi-Harada syndrome (VKH) and Behcet's disease (BD) in a Chinese Han population.

BACKGROUND: Bach2 was reported to play a key role in T lymphocyte development and maturation to mediate immunological homeostasis. Several autoimmune and immune-related diseases were shown to be associated with Bach2 gene polymorphisms. The current study was designed to explore the association between Bach2 gene polymorphism with Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) in a Chinese Han population. METHODS: -427 patients with BD, 422 patients with VKH and 623 controls were recruited for the first stage from a Chinese Han population. The second stage included another set of 388 patients with BD and 460 healthy subjects. PCR fragment length polymorphism methodology was used for genotyping. Frequencies of genotypes and alleles were measured by direct counting and compared between cases and controls by χ(2) test. RESULTS: No difference could be detected between patients suffering from BD or VKH with healthy controls concerning allele and genotype frequencies of rs11755527, rs3757247, rs12212193 and rs2474619. Although in the first stage the frequencies of genotype CC and AC of rs2474619 showed a weak statistical difference between BD and the control group (Pc=0.02), the difference was lost after the second stage and combined stage experiment. CONCLUSIONS: The investigated Bach2 gene polymorphisms (rs11755527, rs3757247, rs12212193 and rs2474619) are not related to the susceptibility to either VKH or BD in our investigated Chinese Han population. CLINICAL TRIAL REGISTRY: This project was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-CCC-12002184).

Association Between Copy Number Variations of TLR7 and Ocular Behçet's Disease in a Chinese Han Population.

PURPOSE: The purpose of this study was to test whether gene copy number variations (CNVs) of Toll-like receptors (TLRs) are associated with uveitis. METHODS: Copy number variations of TLRs were detected by real-time PCR. The first stage of the study consisted of enrolling 400 Behçet's disease (BD) patients, 400 Vogt-Koyanagi-Harada syndrome patients, 400 patients with acute anterior uveitis associated with or without ankylosing spondylitis, and 600 healthy subjects. The second stage included another set of 578 BD patients and 1000 healthy controls. The frequencies of TLR gene copy number types (TLR1, TLR2, TLR3, TLR5, TLR6, TLR7, TLR9, TLR10) were compared among patients and controls by using the χ(2) test. Real-time PCR was used to detect mRNA expression from peripheral blood mononuclear cells (PBMCs) obtained from healthy controls following stimulation with the TLR7 agonist R848. Levels of TNF-α, IL-6, IL-1ß, and IFN-ß in culture supernatants were measured by ELISA. RESULTS: All TLRs tested, except for TLR7, had a gene copy number of two in more than 98% of individuals tested. In the first stage, we found a significantly increased frequency of more than one copy of TLR7 (located on the X chromosome) in male BD patients and more than two copies in female patients (correction of P value [PC] = 0.021; PC = 0.048, respectively). A second stage and combined study confirmed the association (PC = 1.14 × 10(-6); PC = 9.12 × 10(-5), respectively). TLR7 mRNA expression in PBMCs was increased in healthy male carriers having more than one copy of TLR7 or females having more than two copies following stimulation with R848 (P = 0.021, P = 0.006, respectively). No effect of the various TLR7 copies on the release of TNF-α, IL-6, IL-1ß, and IFN-ß could be detected. CONCLUSIONS: This study provides evidence that a high copy number of TLR7 confers risk for BD in a Chinese Han population. (http://www.chictr.org number, ChiCTR-CCC-12002184.).

Renal involvement in Chinese patients with Behcet's disease: a report of 16 cases.

AIM: To investigate the clinical and pathological characteristics of renal involvement in Behcet's disease (BD). METHODS: A retrospective analysis was carried out in BD patients complicated with renal damage who were hospitalized in Peking Union Medical College Hospital from June 1998 to July 2012. RESULTS: There were 16 BD patients with renal involvement, accounted for 2.6% of all the 618 hospitalized BD patients. The presentation of renal disease was chronic glomerulonephritis in six patients (including one with nephritic syndrome), renal tubular acidosis in one patient, renal artery stenosis in eight patients and renal vein thrombosis in one patient. Renal biopsy was performed in five patients, three of whom revealed to have minor glomerular lesions, mild mesangial proliferative glomerulonephritis and chronic tubular-interstitial nephropathy, respectively. The other two patients underwent a second biopsy, the one with minor glomerular lesion in the first biopsy was transformed into grade III immunoglobulin A (IgA) nephropathy on Lee's glomerular grading system 6 years later, and the other one who had IgA nephropathy of grade II in the first biopsy was progressed to grade IV 2 years later. Among the nine patients with renal vascular involvement, two underwent surgery, and several received anticoagulant therapy. During the follow-up of 13 patients, the urine protein quantifications were reduced, and renal function remained relatively stable. CONCLUSIONS: Renal damage is relatively uncommon in BD patients. There are various clinical presentations of renal involvement in BD. Routine screening with urinalysis, serum creatinine and imaging studies should be carried out for the early diagnosis of renal involvement in BD.

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.

Association of ATG5 Gene Polymorphisms With Behçet's Disease and ATG10 Gene Polymorphisms With VKH Syndrome in a Chinese Han Population.

PURPOSE: This study was conducted to explore the association of autophagy-related genes (ATGs) single nucleotide polymorphisms (SNPs) with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. METHODS: A two-stage association study was carried out in 940 BD, 1061 VKH, and 2007 healthy controls. Genotyping for genetic variants of 10 autophagy family genes (ATG5, ATG7, ATG10, ATG16L1, IRGM, LKKR2, ATG2A, DAP, ULK1, and TSC1) was performed using PCR-restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP assays. Gene expression was quantified by real-time PCR. RESULTS: In the cohort of BD patients, we observed that the TT genotype of rs573775/ATG5 decreased susceptibility to BD (Pc = 8.35 × 10-6, OR = 0.490). In the case of VKH patients, the AC genotype of rs4703863/ATG10 increased susceptibility to VKH syndrome (Pc = 9.94 × 10-5, OR = 1.444), whereas the A allele and AA genotype of rs4703863 (Pc = 7.06 × 10-5, OR = 0.745; Pc = 6.34 × 10-6, OR = 0.669, respectively) acted as protective factors for VKH. Functional experiments showed an increased ATG5 expression by LPS stimulated PBMCs in TT cases of rs573775 compared with controls. The level of ATG5 mRNA in active BD patients not receiving immunosuppression was significantly higher than that in healthy controls. CONCLUSIONS: This study demonstrated an association of ATG5 rs573775 with BD and ATG10 rs4703863 with VKH syndrome in a Chinese Han population. Furthermore, a variant of the ATG5 gene was shown to be correlated with ATG5 expression.

Single center study on ethnic and clinical features of Behcet's disease in Moscow, Russia.

For the purpose of investigating Behcet's disease (BD) in Russia, 250 consecutive patients (177 men and 73 women) diagnosed with BD between 1990 and 2010 at the Research Institute of Rheumatology, Russian Academy of Medical Sciences in Moscow were enrolled in this study. The ethnic backgrounds of the patients were reported as follows: 23.2% (58 cases) from Russia, 12.8% (32 cases) from Azerbaijan, 14.4% (36 cases) from Armenia, 8.8% (22 cases) from Chechnya, and 21.6% (55 cases) from Dagestan. The remaining 19.2% (48 cases) were from other regions or of unknown origin. More than half (57.6%) of the Behcet's disease patients originated from Central Asia, specifically Azerbaijan, Armenia, Chechnya, and Dagestan. The mean age at disease onset was 31.5 ± 9.38 (13-60) years old, and the most typical initial manifestations were oral aphthous ulcers. Patients aged 20-39 years old were more commonly affected and displayed a wide clinical spectrum of the disease, with varieties of severe internal organ involvement. The manifestations observed throughout the course of the disease included oral aphthous ulcers (100%), various cutaneous lesions (88.8%), genital ulcers (81.2%), and ocular lesions (54.0%). Besides these, many organs/systems were implicated in patient cases, namely joint (53.2%), vascular (25.2%), neurological (8.0%), gastrointestinal (25.2%), and cardiac (5.6%) systems. Involvements of ocular (p < 0.01) and skin (p < 0.01) lesions were more frequent in men than in women. HLA-B51 and HLA-A26 typing was performed in 127 patients and 508 healthy controls. HLA-B51 was found in 63.0% of BD patients compared to 20.7% of the healthy control subjects (p < 0.001), and HLA-A26 was present in 11.3% of BD patients and 18.9% of the control group. This study shows the presence of BD in Russia, and it is suggested that its prevalence in Central Asian people is much higher than that in White Russian.

Endoscopic findings of gastrointestinal involvement in Chinese patients with Behcet's disease.

AIM: To report the incidence, clinical features and outcomes of gastrointestinal (GI) involvement in Behcet's disease (BD). METHODS: A total of 168 consecutive patients with BD were screened and upper and lower GI endoscopies were performed in 148 patients. Four hundred age- and sex-matched controls were enrolled for comparison. RESULTS: Fifty-two (35.1%) patients had GI lesions. After a mean follow-up of 10 mo, ileocecal ulcers had been confirmed in 20 patients, including active ulcer(s) in 18 patients, but no ileocecal ulceration was found in controls. GI symptoms were present in 14 patients with active ulcer(s), while 4 patients with smaller ulcer were asymptomatic. Endoscopic features of ileocecal ulcer were: a single ulcer (50%), larger than 1 cm in diameter (72.2%), and round/oval or volcano-type in shape (83.3%). Compared with patients without GI involvement, less ocular lesions, lower levels of albumin, erythrocyte count and hemoglobin, and higher levels of C-reactive protein and erythrocyte sedimentation rate were confirmed in the intestinal BD group. Four patients had esophageal ulcers in the BD group but no case in controls. The other endoscopic findings were similar between the two groups. The prevalence of Helicobacter pylori infection was similar in both groups. Most patients received an immunomodulator and responded well. CONCLUSION: GI lesions commonly occur in Chinese BD patients. The most frequently involved area is the ileocecal region. Esophageal ulcer might be a rare but unique lesion.