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.

Comparison of Clinical Features and Visual Outcome between Sympathetic Ophthalmia and Vogt-Koyanagi-Harada Disease in Chinese Patients.

PURPOSE: To characterize the clinical features of sympathetic ophthalmia (SO) and compare SO and Vogt-Koyanagi-Harada (VKH) disease in Chinese patients. DESIGN: Retrospective case series. PARTICIPANTS: A total of 131 consecutive SO and 500 VKH disease patients randomly selected from among those referred to our uveitis center from April 2008 through June 2018. METHODS: History, extraocular and ocular findings, best-corrected visual acuity (BCVA), auxiliary examination findings, complications, and therapeutic effects were analyzed retrospectively in SO and VKH disease patients. MAIN OUTCOME MEASURES: Visual outcome, extraocular and ocular findings, and therapeutic effects. RESULTS: Sympathetic ophthalmia manifested as posterior uveitis (68.8%) within 2 weeks and equal involvement of anterior and posterior segment (44.4%), respectively, was observed between 2 weeks and 2 months after disease onset. Two months after disease onset, SO patients showed sunset glow fundus (51.2%) and granulomatous anterior uveitis (27.3%). Vogt-Koyanagi-Harada disease patients mainly showed posterior uveitis (100%), anterior segment involvement (92.4%) associated with posterior uveitis (84.9%), and granulomatous anterior uveitis (97.4%) accompanying sunset glow fundus (91.5%) in the 3 periods mentioned above. The frequencies of extraocular manifestations were lower in SO patients (24.4%) as compared with VKH disease patients (84.8%; P < 0.001). Best-corrected visual acuity of SO patients improved from 0.68±0.86 logarithm of the minimum angle of resolution (logMAR) to 0.47±0.78 logMAR (P = 0.01), and BCVA of VKH disease patients improved from 0.67±0.79 logMAR to 0.24±0.53 logMAR (P < 0.001) at 12 months of follow-up. A worse BCVA was noted in SO patients compared with VKH disease patients after treatment (P = 0.003). Kaplan-Meier survival analysis showed that the risk of loss of useful vision in SO patients was significantly higher than that of VKH disease patients (P < 0.001). CONCLUSIONS: Chinese SO and VKH disease patients have a different evolutionary process. The frequency of extraocular manifestations in SO patients is much lower as compared with VKH disease patients. Visual outcome is worse in SO as compared with VKH disease.

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.

Promoter Hypermethylation of GATA3, IL-4, and TGF-ß Confers Susceptibility to Vogt-Koyanagi-Harada Disease in Han Chinese.

Purpose: We investigated the role of promoter methylation of transcriptional and inflammatory factors, including TBX21, GATA3, RORγt, FOXP3, IFN-γ, IL-4, IL-17A, and TGF-ß in the development of Vogt-Koyanagi-Harada (VKH) disease. Methods: The promoter methylation levels were detected by the Sequenom MassARRAY system in CD4+ T cells that were separated from 20 healthy individuals and 32 VKH patients (20 in the active stage without medication, 12 in inactive stage with medication). The mRNA expression level of GATA3, IL-4, and TGF-ß in CD4+ T cells was analyzed by real-time RT-PCR. Results: The promoter methylation levels of GATA3, IL-4, and TGF-ß were significantly higher in active VKH patients than in healthy individuals (P < 0.05). A decreased mRNA expression of GATA3 and TGF-ß was found in active VKH patients, which was correlated negatively with the DNA methylation of these factors. Treatment with systemic corticosteroid and cyclosporin A (CsA) decreased the methylation level of GATA3 and TGF-ß in association with an increased mRNA expression of molecules and reduced disease activity. Conclusions: Our findings suggest that promoter hypermethylation of GATA3 and TGF-ß in CD4+ T cells confers risk to VKH disease in Han Chinese.

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.

Clinical Characteristics of Inflammatory Choroidal Neovascularization in a Chinese Population.

PURPOSE: To describe demographic features and clinical and imaging characteristics of inflammatory choroidal neovascularization (CNV) in a Chinese population. METHODS: A retrospective case review of patients with CNV secondary to uveitis from 2002 to 2013. RESULTS: A total of 125 patients (150 eyes, 166 CNVs; bifocal CNVs in 16 eyes), 64% of whom were women, were reviewed. The mean age was 35.86 years. The proportions of patients with punctate inner choroidopathy (PIC), multifocal choroiditis (MFC), and Vogt-Koyanagi-Harada (VKH) were 50.4, 22.4, and 8%. All of the cases were classic CNV in fluorocein angiography and type 2 CNV in OCT. The proportion of subfoveal lesions in active CNV (30.09%) was less than that in inactive CNV (60.38%). CONCLUSIONS: PIC, MFC, and VKH were the three primary specific types of uveitis with inflammatory CNV in this study. Inflammatory CNV tended to break though the retinal pigment epithelium and beneath the neurosensory retina. Moreover, inflammatory CNV was usually nonsubfoveal when it occurred.

Investigation of the association of Vogt-Koyanagi-Harada syndrome with IL23R-C1orf141 in Han Chinese Singaporean and ADO-ZNF365-EGR2 in Thai.

BACKGROUND: We performed a multistage genome-wide association study of Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population and identified two novel non-human leukocyte antigen candidate regions previously. The aim of the study was to replicate the association of IL23R-C1orf141 and ADO-ZNF365-EGR2 with VKH syndrome in four sets of multinational populations in Asia. METHOD: We conducted a candidate genes association study involving 185 patients with VKH syndrome and 287 normal controls from Han Chinese Singaporeans, non-Han Chinese, Thais and Koreans. Genotyping of 16 single nucleotide polymorphisms (SNPs) within IL23R-C1orf141 and ADO-ZNF365-EGR2 loci was performed using the Sequenom MassARRAY system or by Taqman SNP assays. RESULTS: Eight SNPs in IL23R-Clorf141 showed an association with VKH syndrome only in Han Chinese Singaporeans (p=8.49×10(-5) to 1.02×10(-3), pcorrection=1.69×10(-4) to 2.04×10(-3)) but not in the other groups tested. One SNP rs1884444 in IL23R-Clorf141 was found to be weakly associated with VKH syndrome in the Han Chinese Singaporeans, but significance was lost following Bonferroni correction for multiple comparisons. Five SNPs in ADO-ZNF365-EGR2 were found to be associated with VKH syndrome in Thai patients with VKH (p=0.014, pc=0.028) but not in the other three ethnic groups tested. CONCLUSIONS: This study confirmed the genetic associations between SNPs in IL23R-C1orf141 and VKH syndrome in Han Chinese Singaporeans but not in other Asian populations. In addition, we also successfully replicated the association of VKH syndrome with ADO-ZNF365-EGR2 in a Thai population.

Association of ERAP1 Gene Polymorphisms With Behçet's Disease in Han Chinese.

PURPOSE: Behçet's disease (BD) is a common uveitis entity in China. The endoplasmic reticulum aminopeptidase 1 (ERAP1), has a significant influence on the stability and immunological properties of MHC-I loaded peptides. In the present study, we investigated the association of ERAP1 gene polymorphisms with BD in a Chinese Han population. METHODS: A two-stage case-control study was carried out in 930 BD patients and 1704 healthy controls. Seven single nucleotide polymorphisms (SNPs) of the ERAP1 gene were determined using a PCR restriction fragment length polymorphism (PCR-RFLP) assay and one SNP was genotyped by TaqMan SNP genotyping assay. Furthermore, ERAP1 expression in peripheral blood mononuclear cells (PBMCs) was examined in genotyped individuals by real-time PCR. RESULTS: The result demonstrated that the frequencies of the A allele of rs1065407 and C allele of rs10050860 were significantly decreased in BD patients (Pc = 8.5 × 10-8, OR = 0.51; Pc = 1.1 × 10-5, OR = 0.54, respectively). No significant association was observed for the other six SNPs. ERAP1 expression in AA carriers of rs1065407 and CC carriers of rs10050860 was higher than that observed in AC/CC carriers (P = 0.022) or CT/TT carriers (P = 0.018) by LPS-stimulated PBMCs, respectively. In addition, the expression of ERAP1 in active BD patients not receiving immunosuppression was significantly lower than that in healthy controls (P = 3.8 × 10-4). CONCLUSIONS: Our study showed that rs1065407 and rs10050860 of the ERAP1 gene may contribute to the genetic susceptibility of BD by modulating the expression of ERAP1.

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).

Incidence and clinical features of recurrent Vogt-Koyanagi-Harada disease in Japanese individuals.

PURPOSE: Our aim was to determine the recurrence rate of inflammation in Vogt-Koyanagi-Harada (VKH) disease and to describe its clinical features. METHODS: We retrospectively evaluated patients diagnosed as having VKH disease with exudative retinal detachment at the Osaka University Hospital or the Japanese Community Healthcare Organization, Osaka Hospital, between 1998 and 2012. All patients received high-dose corticosteroid therapy as the initial treatment and were followed for at least 6 months. Demographic data, including age, sex, visual acuity (VA) levels at initial presentation and at 1 year after initial therapy, treatment received, and recurrent episodes were reviewed. RESULTS: Fifty-five consecutive patients with VKH disease were identified (36 women; mean age 38.6 ± 10.4 years). Fourteen patients (25.5 %) had recurrent inflammation, which manifested as posterior uveitis in eight and as anterior uveitis in six of the patients. Recurrent posterior segment inflammation was more likely to develop in patients whose VA at initial presentation was poor (P = 0.039) and in whom orally administered corticosteroid was tapered rapidly (to 30 mg within 3 weeks or less, to 20 mg within 2 months or less, and to 10 mg within 3 months or less) (P = 0.006, P = 0.066, and P = 0.041, respectively). CONCLUSIONS: About 25 % of patients with VKH disease had recurrent inflammation. Poor initial VA and rapid tapering of the corticosteroid were associated with posterior recurrence.

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.).

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.

MIF gene polymorphisms confer susceptibility to Vogt-Koyanagi-Harada syndrome in a Han Chinese population.

PURPOSE: The aim of the study was to determine the association of macrophage migration inhibitory factor (MIF) gene polymorphisms with Vogt-Koyanagi-Harada (VKH) syndrome. METHODS: A total of 600 Han Chinese VKH patients and 600 healthy controls were genotyped for rs755622 and rs2096525 of MIF by PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Data were analyzed by χ(2) analysis. RESULTS: Genotype distribution in controls was in Hardy-Weinberg equilibrium. The frequencies of the rs755622 GG genotype and G allele were significantly lower in VKH patients compared with controls (Pc = 0.006 and 0.016). Stratification analysis showed decreased frequencies of the rs755622 GG genotype and G allele in patients, respectively with headache, tinnitus, alopecia, poliosis or vitiligo compared with controls (all Pc < 0.05). rs2096525 genotype and allele frequencies were not different between VKH patients and controls. However, a lower frequency of the rs2096525 TT genotype was observed in patients with headache compared with controls (Pc < 0.05). The frequencies of the rs2096525 T allele in patients with headache or vitiligo were significantly decreased compared with controls (Pc = 8.54 × 10(-4) and 0.012). In addition, the results showed a significantly increased frequency of the combined rs755622/rs2096525 CT haplotype and a decreased frequency of the GT haplotype in VKH patients compared with controls. CONCLUSIONS: Our study identified a strong association of rs755622 with VKH syndrome and certain clinical features. rs2096525 was associated with certain clinical features of VKH syndrome. The results also suggested that the CT and GT haplotypes were associated with VKH syndrome.

[Vogt-Koyanagi-Harada syndrome is an oculo-meningeal syndrome with dermatological and audiological manifestations]. / Vogt-koyanagi-harada er et okulomeningealt syndrom med dermatologiske og audiologiske manifestationer.

Vogt-Koyanagi-Harada syndrome is an autoimmune systemic disease targeting melanin-bearing cells. The disease manifests as a granulomatous inflammatory disease affecting the eyes, meninges, skin and auditory system. The syndrome is common in Japan and Asia but occurs rarely in white Caucasians and has not previously been described in Danish literature. We describe two cases recently seen in a Danish hospital and emphasise the need for early recognition and aggressive treatment of this disease to improve the outcome.

Vogt-Koyanagi-Harada disease in First Nations and Métis of Northern Alberta.

OBJECTIVE: The objective of this article was to describe the incidence, clinical characteristics, and visual outcomes of Vogt-Koyanagi-Harada disease in First Nations and Métis individuals. DESIGN: A retrospective chart review. PARTICIPANTS: Nineteen First Nation and Métis Canadian residents in Northern Alberta. METHODS: Electronic records for a 17-year period (1994-2010) were reviewed. Charts were reviewed for age, sex, length of follow-up, location of primary residence, diagnostic criteria at presentation, disease stage at presentation, duration of symptoms before presentation, ocular and extraocular manifestations at presentation, treatments, compliance, and complications. The time to an eye reaching 20/40, 20/200, and a halving of the baseline visual angle was plotted using Kaplan-Meier methodology. RESULTS: Of 19 First Nations and Métis individuals identified, 84.2% were female, and the average age at presentation was 30.8 years. The most common presenting symptom and sign were blurred vision (89.5%) and anterior segment inflammation (89.5%), respectively. Fifteen (78.9%) patients had extraocular manifestations, the most common being alopecia (26.3%) and cerebrospinal fluid pleocytosis (26.3%). All patients were initially treated with corticosteroids; immunomodulatory therapy was used for 2 (10.5%) patients. Twelve (63.2%) patients experienced ocular complications; 47.4% of patients had difficulty with treatment compliance and attending follow-up appointments. The median time to achieve 20/40 vision was shorter for compliant patients compared with noncompliant patients (P = 0.048). CONCLUSIONS: The features of Vogt-Koyanagi-Harada disease in First Nations and Métis Canadians are most similar to series of South Asian and Hispanic patients. Compliant patients were found to achieve 20/40 vision significantly sooner than noncompliant patients.

TNFAIP3 gene polymorphisms in a Chinese Han population with Vogt-Koyanagi-Harada syndrome.

BACKGROUND: This study was performed to evaluate the potential association of TNFAIP3 polymorphisms with Vogt-Koyanagi-Harada (VKH) disease in a Chinese Han population. METHODOLOGY/PRINCIPAL FINDINGS: Five single-nucleotide polymorphisms (SNPs), rs10499194, rs610604, rs7753873, rs5029928 and rs9494885 of TNFAIP3 were genotyped in 834 VKH disease patients and 1415 healthy controls using a PCR-restriction fragment length polymorphism assay. An increased frequency of the C allele and CT genotype for rs9494885 were found in VKH patients in the Guangzhou and Chongqing cohorts (pc = 0.015, OR = 1.6, pc = 0.036, OR = 1.7; pc = 2.36×10-4, OR = 1.5, pc = 0.012, OR = 1.5, respectively). Meanwhile, a decreased frequency of the TT genotype for rs9494885 was observed in VKH patients in the Guangzhou and Chongqing cohorts (pc = 0.026, OR = 0.6, pc = 0.0074, OR = 0.7, respectively). The combined analysis showed that a significantly increased prevalence of the rs9494885 TC genotype and C allele were found in VKH disease patients compared with controls (pc = 2.26×10-5, OR = 1.7; pc = 1.09× 10-5, OR = 1.6, respectively). The frequency of the TT genotype of rs9494885 was markedly lower in VKH disease patients as compared with that in controls (pc = 1.12×10-5, OR = 0.6; pc = 1.09×10(-5), OR = 0.6, respectively). No association was found between rs10499194, rs610604, rs7753873 and rs5029928 polymorphisms and VKH disease. To our knowledge this is the first report describing the association of a TNFAIP3 gene polymorphism with VKH disease in a Chinese Han population. CONCLUSIONS/SIGNIFICANCE: The results suggest that the rs9494885 TC genotype and C allele may be predisposing factors to VKH disease, whereas the rs9494885 TT genotype and T allele may provide protection against this disease.

JAK1, but not JAK2 and STAT3, confers susceptibility to Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population.

PURPOSE: Janus kinase 1 (JAK1), JAK2, and signal transducer and activator of transcription 3 (STAT3) play an important role in Th1 and Th17 differentiation and gene polymorphisms of these factors have been demonstrated to be associated with certain autoimmune diseases. The present study was performed to assess the association between JAK1, JAK2, and STAT3 polymorphisms and Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population. METHODS: A case-control study was performed in 737 Chinese VKH syndrome patients and 809 healthy controls from a Han Chinese population. The genotypes of three single-nucleotide polymorphisms (SNPs) (rs310230, rs310236, rs310241) in JAK1 were performed using an SNP genotyping system. Three SNPs (rs10758669, rs7857730, rs10119004) in JAK2 and four SNPs (rs6503695, rs744166, rs2293152, and rs12948909) in STAT3 were analyzed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Hardy-Weinberg equilibrium (HWE) was tested using the χ(2) test. Genotype frequencies were estimated through direct counting. Allele and genotype frequencies were compared between patients and controls using the χ(2) test. RESULTS: There was no deviation from the HWE in all controls tested. Three SNPs, including rs310230, rs310236, and rs310241, in JAK1 were significantly associated with VKH syndrome (Pc = 0.008, 0.005, 0.001, respectively). None of the tested SNPs of JAK2 and STAT3 was associated with VKH syndrome. Stratification analysis according to headache, dysacusis, alopecia, poliosis, and vitiligo for VKH syndrome did not reveal an association. CONCLUSIONS: These results suggest that JAK1 genetic polymorphisms, but not JAK2 and STAT3, are associated with the susceptibility to VKH syndrome.

Association analysis of TGFBR3 gene with Vogt-Koyanagi-Harada disease and Behcet's disease in the Chinese Han population.

OBJECTIVES: Transforming growth factor-ß (TGF-ß) has important regulating roles in the immune system, especially in the differentiation of the type 17 helper T cells (Th17 cells). In this study, we analysed the potential association of the type III TGF-ß receptor (TGFBR3) genetic variations (rs2489188 and rs1805110) in the Chinese Han population for patients with either Vogt-Koyanagi-Harada (VKH) disease or Behcet's disease (BD), two uveitis entities presumably mediated by Th17 cells. METHODS: Two single-nucleotide polymorphisms (SNPs), rs2489188 and rs1805110, in TGFBR3 were genotyped in 451 VKH patients, 330 BD patients and 468 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism assay. The association of the two SNPs with both diseases was analysed using the chi-square test. The Bonferroni correction was applied for multiple testing. A binary logistic regression analysis was used to assess the influence of the gender on the association of TGFBR3 polymorphisms with BD. RESULTS: A significantly decreased frequency of rs1805110 CC genotype (corrected P (P(c)) = 0.03, odds ratio = 0.617, 95% CI = 0.441-0.863) was observed in BD patients compared with controls. After logistic regression analysis, this association was maintained (P(c) = 0.036). Frequencies of genotype and allele of rs2489188 were not different between VKH disease or BD patients and controls. Stratification analysis according to clinical features of VKH disease or BD failed to find any association of the tested SNPs with both diseases. CONCLUSIONS: The results suggest that rs1805110 CC genotype in TGFBR3 is probably associated with the protection from BD. The tested two TGFBR3 SNPs are not associated with VKH disease.