title: Association of TLR2 gene polymorphisms with ocular Behcet's disease in a Chinese Han population.
abstract: OBJECTIVE
  TLR2, TLR4, TLR8, and TLR9 have been reported to be associated with several autoimmune diseases. The current study aimed to explore whether singe nucleotide polymorphisms (SNPs) of these four genes were associated with ocular Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis (AAU) with or without ankylosing spondylitis (AS), or pediatric uveitis in Han Chinese.
  
  
  METHODS
  Genotyping was performed by PCR-restriction fragment length polymorphism. The first stage study comprised 400 ocular BD patients, 400 VKH syndrome patients, 400 AAU ± AS patients, 400 pediatric uveitis patients and 600 healthy subjects. The second stage included 438 ocular BD patients and 1000 healthy subjects. Allele and genotype frequencies were compared between patients and controls using the χ(2) test. Real-time PCR was used to detect mRNA expression from PBMCs obtained from healthy controls. Levels of TNF-α, IL-6, IL-10, and IL-1beta in culture supernatants were measured by ELISA.
  
  
  RESULTS
  In the first stage study, only the frequencies of the rs2289318/TLR2 genotype A and C allele and rs3804099/TLR2 genotype CT were significantly higher in ocular BD patients (Pc = 0.048; Pc = 0.008; Pc = 0.005, respectively) compared with controls. The second stage and combined studies confirmed the association (Pc = 0.001; Pc = 6.89E-06, Pc = 2.426E-06, respectively). TLR2 mRNA expression in PBMCs was increased in healthy carriers of the CC genotype of rs2289318/TLR2 and TT genotype of rs3804099/TLR2 following stimulation with peptidoglycan (PGN; P = 0.028; P = 0.004, respectively). No effect of the various TLR2 rs2289318 and rs3804099 genotypes on the release of TNF-α, IL-6, IL-10, and IL-1beta could be detected.
  
  
  CONCLUSIONS
  This study provides evidence that the TLR2 gene is involved in the susceptibility to ocular BD.
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.forename: Ranran
authors.initials: R
authors.lastname: Hu
authors.forename: Shengping
authors.initials: S
authors.lastname: Hou
authors.forename: Zi
authors.initials: Z
authors.lastname: Ye
authors.forename: Qin
authors.initials: Q
authors.lastname: Xiang
authors.forename: Jian
authors.initials: J
authors.lastname: Qi
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D001528:Behcet Syndrome / Q000235:genetics*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013167:Spondylitis, Ankylosing / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051200:Toll-Like Receptor 8 / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics; D014607:Uveomeningoencephalitic Syndrome / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9
keywords: Behçet's disease; TLR2; TLR4; TLR8; TLR9; TLRs; VKH syndrome; acute anterior uveitis; ankylosing spondylitis; pediatric uveitis