Two Genetic Variations in the IRF8 region are associated with Behçet’s disease in Han Chinese

Abstract

Several modulatory factors in the TLR signaling pathway including IRF3, IRF7, IRF8, TRIM20, MYD88 and NF-κB1 have been associated with autoimmune disease. In this study, we investigated the association of 13 SNPs for these genes with Behçet’s disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Haplotype and linkage disequilibrium (LD) analysis were performed by Haploview4.2. IRF8 mRNA expression and cytokine production was tested by real-time PCR and ELISA. Two SNPs near IRF8 were associated with BD (for rs17445836 GG genotype, Pc = 9.56 × 10−8, OR = 2.044; for rs11642873 AA genotype, Pc = 9.24 × 10−7, OR = 1.776). No significant association was found for the 13 SNPs tested with VKH syndrome. Haplotype analysis of the two positive SNPs revealed that the AG haplotype was significantly increased in BD patients (Pc = 2.60 × 10−8, OR = 1.646). Functional studies revealed an increased mRNA expression of IRF8 and IFN-γ production and a decreased production of IL-10 in rs17445836 carriers with the GG genotype. Increased expression of IRF8 as well as IFN-γ production and a decreased production of IL-10 were found in individuals carrying the rs11642873/AA genotype. In conclusion, this study indicates that IRF8 may contribute to the genetic susceptibility of BD by regulating IRF8 expression and cytokine production.

Comparing domain wall synapse with other non volatile memory devices for on-chip learning in analog hardware neural network

“…Verilog-A model provided by [40], experimentally benchmarked against [41], has been used for RRAM modeling. Following the 1T1M (one transistor, one memristor) configuration [42,43,44] we connect this RRAM device with a 65 nm technology node transistor (from UMC library) in Cadence Virtuoso circuit simulator ( Fig. 4(a)).…”

Genetics of Behçet’s Disease

“…In particular, it regulates expression of type I IFN stimulated genes [75], and interacts with the Th17 master transcription factor, ROR-γt to inhibit Th17 cell differentiation [76]. In a study with Chinese cohort, the IRF8 SNPs rs17445836 and rs11642873 were associated with BD, and they appeared to regulate IRF8 expression and corresponding cytokine production [77]. In another study with multiple cohorts including Turkish, Iranian, and Japanese patients, three other BD-associated SNPs (rs11117433, rs142105922 and rs7203487) of the IRF8 gene were reported [78].…”

Genetic aspects of idiopathic paediatric uveitis and juvenile idiopathic arthritis associated uveitis in Chinese Han

“…Our results are consistent with earlier reports in JIA, 33 showing that the G allele and GG genotype of rs224217 act as protective factors. This variant was also investigated in inflammatory bowel disease 51 and BD, 52 but no significant associations were found. Other variants of MEFV (rs224224 and rs224223) have been shown to be associated with familial Mediterranean fever.…”