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Behçet's disease (BD) is a systemic and inflammatory disease, characterized mainly by recurrent oral and genital ulcers, eye involvement, and skin lesions. Although the exact etiopathogenesis of BD remains unrevealed, a bulk of studies have implicated the genetic contributing factors as critical players in disease predisposition. In countries along the Silk Road, human leukocyte antigen (HLA)-B51 has been reported as the strongest genetically associated factor for BD. Genome-wide association studies, local genetic polymorphism studies, and meta-analysis of combined data from Turkish, Iranian, and Japanese populations have also identified new genetic associations with BD. Among these, other HLA alleles such as HLA-B*15, HLA-B*27, HLA-B*57, and HLA-A*26 have been found as independent risk factors for BD, whereas HLA-B*49 and HLA-A*03 are independent protective alleles for BD. Moreover, other genes have also reached the genome-wide significance level of association with BD susceptibility, including IL10, IL23R-IL12RB2, IL12A, CCR1-CCR3, STAT4, TNFAIP3, ERAP1, KLRC4, and FUT2. Also, several rare nonsynonymous variants in TLR4, IL23R, NOD2, and MEFV genes have been reported to be involved in BD pathogenesis. According to genetic determinants in the loci outside the MHC region that are contributed to the host defense, immunity, and inflammation pathways, it is suggested that immune responses to the pathogen as an important environmental factor and mucosal immunity contribute to BD susceptibility. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: It has been hypothesized that dysfunction of the solute carrier family 1, member1 gene (SLC1A1), which encodes the glutamate aspartate transporter, may play a role in normal tension glaucoma. In this study we investigate whetherSLC1A1is associated with normal tension glaucoma in Japanese patients. Methods: A total of 292 Japanese patients with normal tension glaucoma and 500 healthy control subjects were recruited. We genotyped 12 single-nucleotide polymorphisms inSLC1A1. We also performed an imputation analysis to evaluate the potential association of un-genotypedSLC1A1single-nucleotide polymorphisms, and 165 single-nucleotide polymorphisms were imputed. Results: We observed an increased frequency of the G allele of rs10739062 in patients compared to controls (p = 0.043, OR = 1.25). The rs10739062 polymorphism exhibited a dominant effect: individuals with genotype GG and GC showed a 1.91-fold increase in risk compared to genotype CC (p = 0.0082). However, the statistical significance disappeared after Bonferroni correction for multiple testing (pc > 0.05). We did not find any significant association between any of the remaining 176 single-nucleotide polymorphisms and disease risk. Conclusions: Our study showed a lack of association betweenSLC1A1variants and normal tension glaucoma in Japanese patients, suggesting that theSLC1A1gene does not play a critical role in the development of the disorder in this patient population. However, further genetic studies with larger sample sizes are needed to clarify whetherSLC1A1may make some contribution that affects the risk of developing normal tension glaucoma. [ABSTRACT FROM PUBLISHER]

Diagnosis and treatment of Behçet's disease (BD) have continued to undergo new changes in recent years. We organized a Compilation Committee for Guidelines on Diagnosis and Treatment of Ocular Behçet's Disease with five ophthalmology research facilities in Japan (Hokkaido University, Health Sciences University of Hokkaido, University of Tokyo, Tokyo Medical University, and Yokohama City University), and accomplished the Major review of Current aspects of Ocular Behçet's Disease in Japan. The review consist of four chapters: introduction, ocular lesions, diagnosis, and treatment. We are very pleased if the guidelines are found to be effective and useful in improving the quality of life (QOL) and quality of vision (QOV) of BD patients in the world. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents a study to identify the role of toll-like receptors 9 (TLR9) gene polymorphisms in the development of sarcoidosis by evaluating the association between TLR9 polymorphisms and sarcoidosis in Japanese patients. It mentions presence of TLR9 gene on chromosome 3p21 and use of single-nucleotide polymorphisms (SNPs). The study concludes a lack of association between TLR9 polymorphisms and Japanese sarcoidosis.