Alteration of oral flora in Mongolian patients with Behçet's disease: a multicentre study.

OBJECTIVES: Behçet's disease (BD) is characterised by repeated acute inflammatory attacks with aphthous ulcers of the oral mucosa, uveitis of the eyes, skin symptoms, and genital ulcers. Although its aetiology is still unknown, there is evidence of the involvement of oral bacteria in systemic diseases. Various types of oral bacteria may be involved in the development and progression of BD. The present study investigated alterations in the oral flora of patients with BD in Mongolia. We collected saliva samples from the Mongolian BD group and healthy control (HC) group, and the oral flora were analysed using next-generation sequencer (NGS). METHODS: DNA was extracted from the unstimulated saliva samples from the 47 BD and 48 HC subjects. The DNA was amplified from the V3-V4 region of 16S rRNA using PCR, and the data were acquired using NGS. Based on the obtained data, we analysed the alpha diversity, beta diversity, and bacterial taxonomy of the salivary flora. RESULTS: Beta diversity differed significantly between the BD and HC flora, but no significant differences were observed in alpha diversity. We found that the proportions of three genera - an S24-7 family unknown species, a mitochondria family unknown species, and Akkermansia species associated with IL-10 production - were significantly lower in the BD than in the HC group. CONCLUSIONS: The reduced proportions of the S24-7 family and symbiotic Akkermansia species may be key phenomena in the oral flora of patients with BD.

Variants in IL23R-C1orf141 and ADO-ZNF365-EGR2 are associated with susceptibility to Vogt-Koyanagi-Harada disease in Japanese population.

Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.

Clinical features of Behcet's disease in Mongolia: a multicenter study.

OBJECTIVE: The aim of the present study is to investigate the clinical features of patients with Behcet's disease (BD) in Mongolia. METHODS: Patients were identified and examined from six medical institutions in Mongolia from January 2015 to January 2019. BD was diagnosed according to the diagnostic criteria for BD established by the International Study Group. RESULTS: There were sixty-five patients (22 males and 43 females) recoded, the ratio of 1:1.95, with a marked female predominance. The age of disease onset was 22.2 ± 10.0 (mean ± SD), ranging from 11 to 66 years old. Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, pathergy test positivity, articular lesions, superficial vasculitis, deep vein thrombosis, and epididymitis (male only) were observed in 100.0%, 63.1%, 81.5%, 89.2%, 7.7%, 86.2%, 32.3%, 4.6%, and 13.6% of the patients, respectively. The incidence of poor visual prognosis, ≤ 20/200, was significantly higher in males than in females (31.8 vs. 9.3%, incidence rate ratio 4.55 (95% CI 1.16-17.82), p < 0.05). The pathergy test was positive only in 7.7% of cases and only in female subjects. Nasal mucous ulcers were frequently seen in 55.4% of patients that may also be attributed to the environmental conditions of Mongolia. Headache was observed 76.9% of patients in this study. CONCLUSIONS: Clinical manifestations of BD in Mongolia are presented for the first time. The visual prognosis was significantly worse in males. Nasal mucous membrane ulcers and recurrent headaches were frequent among Mongolian patients with BD. Key Points • First results of the examination of the clinical features of Behcet's disease patients in Mongolia. • Nasal ulcerations and recurrent headaches are frequent symptoms in Mongolia Behcet's disease patients, potentially attributed to climate. • Male Behcet's disease patients in Mongolia have a significantly worse prognosis for eye-related complications and vision.

The influence of HLA-B51 on clinical manifestations among Japanese patients with Behçet's disease: A nationwide survey.

Objectives: To scrutinize the influence of HLA-B51 to each clinical manifestation of patients with Behçet's disease (BD) using a database of the Ministry of Health, Labour and Welfare of Japan.Methods: The database of newly registered patients with BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met International Criteria for Behçet's Disease (ICBD) and had data for HLA-B51 were selected and analyzed.Results: Among the 3044 analyzable cases, 1334 (43.8%) were men and 1710 (56.2%) were women; the median age was 38 years (IQR 29-48). HLA-B51 was positive for 1334 (44.5%). Prevalence of selected manifestations was 98.5% for oral ulceration, 85.5% for skin lesion, 42.1% for ocular lesion, 69.1% for genital ulceration, and 29.0% for gastrointestinal symptom. HLA-B51-positive patients had higher risk for ocular lesion (OR 1.59, 95%CI: 1.37-1.84; p < .001) and lower risk for genital ulceration (OR 0.72, 95%CI: 0.62-0.84; p < .001) and gastrointestinal symptom (OR 0.65, 95%CI: 0.55-0.77; p < .001). No significant difference was observed for other organ involvement; oral ulceration, skin lesion, positive pathergy test, arthritis, epididymitis, vascular lesion, or neurological manifestation. Subgroup analyses revealed that HLA-B51 was not related to genital ulceration in the cases with an ICBD score of 6 or higher and that HLA-B51 tended to more largely affect the risk of three manifestations for men compared to that for women.Conclusion: HLA-B51 positive is a risk factor for ocular lesion and vice versa for genital ulceration and gastrointestinal symptoms in patients with Japanese BD.

Association Study of ARMC9 Gene Variants with Vogt-Koyanagi-Harada Disease in Japanese Patients.

Purpose: To investigate whether variants in the ARMC9 gene encoding KU-MEL-1 are associated with Vogt-Koyanagi-Harada (VKH) disease in a Japanese population. Methods: We recruited 380 Japanese patients with VKH disease and 744 Japanese healthy controls to genotype seven single-nucleotide polymorphisms (SNPs) in ARMC9. We also performed imputation analysis of the ARMC9 region and 195 imputed SNPs were included in the statistical analysis. Results: We observed an increased frequency of the A allele of rs28690417 in patients compared with controls (P = 0.0097, odds ratio (OR) = 1.46). The A allele had a dominant effect on VKH disease risk (P = 0.011, OR = 1.51). However, these significant differences disappeared after Bonferroni correction (corrected P > 0.05). The remaining 201 SNPs did not show any significant association with disease risk. Conclusions: Our study suggests that ARMC9 variants do not play a critical role in the development of VKH disease.

A Randomized, Placebo-Controlled Study on the Safety and Efficacy of Daily Ingestion of Green Tea (Camellia sinensis L.) cv. "Yabukita" and "Sunrouge" on Eyestrain and Blood Pressure in Healthy Adults.

The green tea (Camellia sinensis L.) cultivar “Sunrouge” contains anthocyanins, catechins and flavonols. To determine whether ingesting green tea containing anthocyanins improves visual function and blood pressure (BP) in healthy adults, a randomized, double-blind, placebo-controlled study was performed. A total of 120 healthy subjects, aged between 20 and 60 years and with a systolic BP (SBP) value of ≤125 and <155 and a diastolic BP (DBP) value <95, or a DBP of ≤75 mmHg and <95 mmHg and a SBP <155 mmHg, were randomly assigned to one of three groups. For 12 weeks, the placebo group received barley extract without catechin; another group received “Sunrouge” extract containing 11.2 mg anthocyanin and 323.6 mg epigallocatechin-3-O-gallate (EGCG); and a third group received “Yabukita” extract containing 322.2 mg EGCG. Home BP, accommodation ability, visual analog scale questionnaires for eyestrain, and metabolic-associated markers were analyzed at weeks 0, 4, 8, and 12 of the intake period. The ingestion of “Sunrouge” tea significantly improved accommodation ability and eyestrain in subjects younger than 45 years and in subjects who operated visual display terminals every day. It also elevated BP. “Yabukita” tea ingestion significantly increased serum adiponectin levels. No adverse effects were observed. We conclude that long-term intake of “Sunrouge” tea containing anthocyanins and flavonols might improve visual function.

Protective Effects of Oral Astaxanthin Nanopowder against Ultraviolet-Induced Photokeratitis in Mice.

PURPOSE: Astaxanthin (AST) has a strong antioxidant cellular membrane chaperone protective effect. Recently, a water-soluble nanosized AST (nano-AST) form was produced, which is expected to improve the efficacy of oral intake effects. The purpose of this study was to examine whether oral nano-AST has therapeutic effects on UV-induced photokeratitis in mice. METHODS: C57BL/6 mice were administered twice with either nano-AST, AST oil, lutein, or bilberry extracts 3 hours before and shortly before UV irradiation (dose: 400 mJ/cm2). The corneas were collected 24 hours after irradiation and stained with H&E and TUNEL. NF-κB, dihydroethidium (DHE), COX-2, p-IκB-α, TNFα, and CD45 expression were evaluated through immunohistochemistry, Western blot analysis, and qPCR. RESULTS: Corneal epithelium was significantly thicker in mice orally administered with nano-AST than in the others (p < 0.01), with significantly less NF-κB nucleus translocation (p < 0.001), and significantly fewer TUNEL cells (p < 0.01). Weaker DHE signals were detected in the nano-AST group (p < 0.05) relative to the others. Furthermore, reduced inflammation and decreased cell death in corneal tissue were observed in the nano-AST group, as indicated by a reduction in the expression of COX-2, p-IκB-α, TNFα, and CD45. CONCLUSIONS: Oral administration of nano-AST demonstrated a protective effect on UV-induced photokeratitis via antioxidative, anti-inflammatory, and antiapoptotic activity.

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.

Serial Frequencies and Clinical Features of Uveitis in Hokkaido, Japan.

PURPOSE: Environmental and lifestyle changes influence the clinical features of uveitis. This study reviewed the epidemiologic trends of uveitis in the Japanese population. METHODS: A retrospective review of the past 80 years of reports from Hokkaido University Hospital. RESULTS: In the 1930s, tuberculosis accounted for 46% and syphilitic uveitis for 31% of cases. The frequency of these diseases decreased to 12% in the 1950s; 8% in 1969; 0.6% in the 1990s; and 0.8% in the 2000s, while the rate of non-infectious uveitis increased. The three most common specific diagnoses were: sarcoidosis, Vogt-Koyanagi-Harada disease, and Behçet disease. Although Behçet disease was the most frequent non-infectious uveitis until the 1980s, sarcoidosis is now the most frequent cause of newly diagnosed non-infectious uveitis. CONCLUSIONS: The etiology of uveitis has changed with the times. Tubercular and syphilitic cases have greatly decreased, and sarcoidosis is the most frequent type of uveitis today.

Ocular Behçet's disease is less complicated with allergic disorders. A nationwide survey in Japan.

OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. METHODS: The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). RESULTS: Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. CONCLUSIONS: Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.

Trabecular meshwork depigmentation in Vogt-Koyanagi-Harada disease.

PURPOSE: Since some patients develop depigmentation of the trabecular meshwork in the course of Vogt-Koyanagi-Harada (VKH) disease, we examined the incidence of trabecular depigmentation and its correlation with other ocular findings and systemic symptoms. METHODS: We retrospectively reviewed the clinical charts of 53 Japanese patients diagnosed with VKH disease. The scores of trabecular and limbal pigmentation of all patients were recorded. We then examined the correlation between trabecular pigmentation and the presence of sunset glow fundus or skin lesions. RESULTS: Trabecular pigmentation was significantly lower in the patients with sunset glow fundus than in those without it (P = 0.022), whereas limbal pigmentation showed no significance. However, there were no significant differences in trabecular and limbal pigmentation between the patients with and those without skin lesions. Furthermore, there was no correlation between trabecular and limbal pigmentation. CONCLUSIONS: Depigmentation of the trabecular meshwork develops in some patients in the course of VKH disease. This depigmentation is significantly correlated with sunset glow fundus, but not with limbal depigmentation or skin lesions.

Induction of heat shock protein 70 ameliorates ultraviolet-induced photokeratitis in mice.

Acute ultraviolet (UV) B exposure causes photokeratitis and induces apoptosis in corneal cells. Geranylgeranylacetone (GGA) is an acyclic polyisoprenoid that induces expression of heat shock protein (HSP)70, a soluble intracellular chaperone protein expressed in various tissues, protecting cells against stress conditions. We examined whether induction of HSP70 has therapeutic effects on UV-photokeratitis in mice. C57 BL/6 mice were divided into four groups, GGA-treated (500 mg/kg/mouse) and UVB-exposed (400 mJ/cm2), GGA-untreated UVB-exposed (400 mJ/cm2), GGA-treated (500 mg/kg/mouse) but not exposed and naive controls. Eyeballs were collected 24 h after irradiation, and corneas were stained with hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). HSP70, reactive oxygen species (ROS) production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and protein kinase B (Akt) expression were also evaluated. Irradiated corneal epithelium was significantly thicker in the eyes of mice treated with GGA compared with those given the vehicle alone (p < 0.01). Significantly fewer TUNEL-positive cells were observed in the eyes of GGA-treated mice than controls after irradiation (p < 0.01). Corneal HSP70 levels were significantly elevated in corneas of mice treated with GGA (p < 0.05). ROS signal was not affected by GGA. NF-κB activation was reduced but phospho-(Ser/Ther) Akt substrate expression was increased in corneas after irradiation when treated with GGA. GGA-treatment induced HSP70 expression and ameliorated UV-induced corneal damage through the reduced NF-κB activation and possibly increased Akt phosphorilation.

Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet's disease.

OBJECTIVES: To identify non-major histocompatibility complex susceptible genes that might contribute to Behçet's disease (BD). METHODS: We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated. RESULTS: We found a novel association of BD to the GIMAP locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01×10(-8) in a minor allele dominant model; rs11769828, allele based p=1.60×10(-6)). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70×10(-6)) in GIMAP4; rs10266069 (OR=1.32, p=2.67×10(-4)) and rs10256482 (OR=1.27, p=5.27×10(-4)) in GIMAP2; and rs2286900 (OR=1.61, p=3.53×10(-5)) in GIMAP1 areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the GIMAP locus. The GIMAP4 promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of GIMAP4 mRNA, and GIMAP4 knockdown was protective against Fas-mediated apoptosis. CONCLUSIONS: These results suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development 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.

Investigation of association between TLR9 gene polymorphisms and VKH in Japanese patients.

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder affecting melanocytes in the skin, eyes, inner ear, and meninges. The Epstein-Barr virus and cytomegalovirus (CMV) antigen have been hypothesized as possible triggering factors for the disease. Toll-like receptors (TLRs) play an important role in the induction of defense mechanisms of the innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR9 recognizes unmethylated 2'-deoxyribo (cytidine-phosphate guanosine)(CpG) DNA motifs that are frequently present in viruses and plays a central role in the host defense against viral infection. The aim of this study was to investigate whether TLR9 polymorphisms were associated with VKH in a Japanese population. METHODS: Ninety-four Japanese patients diagnosed with VKH and 125 healthy control subjects were recruited. Five single-nucleotide polymorphisms (SNPs: rs187084, rs5743836, rs352139, rs352140, rs5743845) in the TLR9 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects. RESULTS: Strong linkage disequilibrium was observed among three SNPs (D' > 0.99), which were located in one haplotype block. Two SNPs (rs5743836 and rs5743845) were monopolymorphic in both cases and controls. No statistically significant association was observed for any of the SNPs between cases and controls. CONCLUSION: Three SNPs in the TLR9 gene were not significantly associated with susceptibility to VKH.

Evaluation of NLRP1 gene polymorphisms in Vogt-Koyanagi-Harada disease.

PURPOSE: Polymorphisms of the NACHT [neuronal apoptosis inhibitory protein (NAIP), CIITA, HET-E, TP1] and leucine-rich repeat protein 1 (NLRP1) gene are reported to be associated with susceptibility to vitiligo and several autoimmune diseases. Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder affecting melanocytes in the skin, eyes, inner ear, and meninges. In this study, genetic associations between VKH disease and single-nucleotide polymorphisms (SNPs) surrounding the NLRP1 gene were investigated. METHODS: Six SNPs (rs6502867, rs925597, rs3926687, rs2733359, rs878329, and rs4790796) near the NLRP1 gene, including noncoding regions, were sequenced by a direct method to genotype 167 Japanese patients with VKH disease and 187 healthy Japanese volunteers. RESULTS: None of the six SNPs in the NLRP1 region were significantly associated with disease susceptibility or the ocular, neurological, and dermatological manifestations of VKH. CONCLUSIONS: Although skin manifestations are clinically similar between vitiligo and VKH disease, the genetic and immunological mechanisms of these two diseases may be different.

Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci.

Behçet's disease is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent ocular symptoms, oral and genital ulcers and skin lesions. We conducted a genome-wide association study in a Japanese cohort including 612 individuals with Behçet's disease and 740 unaffected individuals (controls). We identified two suggestive associations on chromosomes 1p31.3 (IL23R-IL12RB2, rs12119179, P = 2.7 x 10(-8)) and 1q32.1 (IL10, rs1554286, P = 8.0 x 10(-8)). A meta-analysis of these two loci with results from additional Turkish and Korean cohorts showed genome-wide significant associations (rs1495965 in IL23R-IL12RB2, P = 1.9 x 10(-11), odds ratio = 1.35; rs1800871 in IL10, P = 1.0 x 10(-14), odds ratio = 1.45).

Evaluation of PTPN22 polymorphisms and Vogt-Koyanagi-Harada disease in Japanese patients.

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder against melanocytes. Polymorphisms of the protein tyrosine phosphatase non-receptor 22 gene (PTPN22) have recently been reported to be associated with susceptibility to several autoimmune diseases. In this study, genetic susceptibility to VKH disease was investigated by screening for single nucleotide polymorphisms (SNPs) of PTPN22. METHODS: A total of 167 Japanese patients with VKH disease and 188 healthy Japanese controls were genotyped by direct sequencing methods for six SNPs (rs3811021, rs1217413, rs1237682, rs3761935, rs3789608, and rs2243471) of PTPN22 including the uncoding exons. RESULTS: The six SNPs in PTPN22 showed no significant association with susceptibility to VKH disease or its ocular, neurologic, or dermatological manifestation. CONCLUSIONS: Further studies are needed to clarify the genetic mechanisms underlying VKH disease.

Association of TLR4 polymorphisms with Behcet's disease in a Korean population.

OBJECTIVES: HLA-B51 is strongly associated with Behçet's disease (BD) in any ethnic background. We recently reported that another gene, Toll-like receptor-4 (TLR4) is also implicated in BD in a Japanese population. To confirm these results, we investigated polymorphisms in the TLR4 gene in Korean patients with BD. METHODS: In this study, 119 patients with BD and 141 healthy controls were enrolled; every participant was a Korean. Nine single nucleotide polymorphisms previously detected in TLR4 by direct sequencing were analysed for an association with BD. RESULTS: The most frequent haplotype, TAGCGGTAA, was significantly increased in HLA-B*51-positive BD patients (49.5%), compared with healthy control participants [32.3%; P = 0.029; odds ratio (OR) = 2.01; 95% CI 1.25-3.23]. This haplotype was also significantly increased in BD patients with arthritis (48.2%; P = 0.003; OR = 1.96; 95% CI 1.26-3.26). There were no significant differences in the allele and genotype frequencies of patients and controls for each single nucleotide polymorphism. CONCLUSIONS: The haplotype of TLR4 may increase the risk for developing BD and the complication of arthritis in the Korean population.