title: TRAF5 and TRAF3IP2 gene polymorphisms are associated with Behçet's disease and Vogt-Koyanagi-Harada syndrome: a case-control study.
abstract: BACKGROUND
  TRAF5 and TRAF3IP2 have been reported to be associated with several autoimmune diseases. Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome are two autoimmune uveitis entities whereby both genetic and environmental factors are thought to be involved.
  
  
  OBJECTIVE
  The role of TRAF5 and TRAF3IP2 in BD and VKH has not yet been reported and was therefore the subject of this study.
  
  
  METHODS
  The study included 789 BD patients, 940 VKH patients and 1601 healthy unrelated individuals. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or TaqMan® SNP Genotyping Assay. Real-Time PCR was used to detect mRNA expression from PBMCs obtained from healthy controls with (n = 22) or without (n = 79) stimulation. Levels of TNF-α, IL-6 and IL-8 in culture supernatants were measured by ELISA (n = 22).
  
  
  RESULTS
  Three SNPs (rs6540679, rs12569232, rs10863888) of TRAF5 and rs13210247 of TRAF3IP2 were significantly associated with Behçet's disease and VKH syndrome (corrected P values ranging from 9.45×10(-12) to 0.027). TRAF3IP2 rs33980500 and rs13190932 were not polymorphic in Han Chinese. Following stimulation by lipopolysaccharide (LPS), carriers of the GG genotype of rs6540679/TRAF5 had a higher TRAF5 mRNA expression (p = 0.004) and an increased TNF-α (p = 0.0052) and IL-6 (p = 0.0014) level compared with AA and AG genotype carriers.
  
  
  CONCLUSIONS
  This study provides evidence that TRAF5 and TRAF3IP2 genes are involved in the development of BD and VKH syndrome. Functional research suggested that TRAF5 gene polymorphisms may regulate TRAF5 expression and downstream inflammatory cytokines such as TNF-α and IL-6.
authors.affiliation: Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute; The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute; The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute; The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Shengping
authors.initials: S
authors.lastname: Hou
authors.affiliation: Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute; The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute; The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute; The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Bai
authors.affiliation: Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute; The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Yunjia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: University Eye Clinic Maastricht, Maastricht, The Netherlands.
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
authors.affiliation: Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute; The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001528:Behcet Syndrome / Q000235:genetics*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D048015:TNF Receptor-Associated Factor 5 / Q000235:genetics*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000235:genetics*; D014607:Uveomeningoencephalitic Syndrome / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D048015:TNF Receptor-Associated Factor 5; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins