title: MicroRNA-146a and Ets-1 gene polymorphisms in ocular Behcet's disease and Vogt-Koyanagi-Harada syndrome.
abstract: OBJECTIVE
  MicroRNA-146a (miR-146a) is involved in certain immune-mediated diseases. Transcription factor Ets-1 strongly affects miR-146a promoter activity and directly regulates miR-146a expression. This study was performed to investigate the association of miR-146a and Ets-1 gene polymorphisms with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) disease in a Chinese Han population.
  
  
  METHODS
  A total of 809 patients with BD, 613 patients with VKH and 1132 normal controls were genotyped for miR-146a/rs2910164, rs57095329 and rs6864584, Ets-1/rs1128334 and rs10893872 using a PCR restriction fragment length polymorphism assay. miR-146a expression was examined in peripheral blood mononuclear cells (PBMCs) by real-time PCR. Cytokine production by PBMCs was measured by ELISA.
  
  
  RESULTS
  A significantly decreased frequency of the homozygous rs2910164 CC genotype and C allele was observed in patients with BD compared with controls (pc(a)=1.24×10(-5), OR 0.61; pc(a)=1.33×10(-4), OR 0.75, respectively). MiR-146a expression in GG cases was 2.45-fold and 1.99-fold higher, respectively, than that in CC cases and GC cases. There was no association of the other four single nucleotide polymorphisms (SNPs) with BD. There was also no association of these five SNPs with its main clinical features. No associations were found with the five SNPs tested or with its clinical manifestations in VKH disease. Interleukin (IL)-17, tumour necrosis factor (TNF)α and IL-1β production from rs2910164 CC cases was markedly lower than that in GG cases. No effect of genotype was observed on IL-6 and monocyte chemoattractant protein (MCP)-1 production and IL-8 expression was slightly higher in CC cases.
  
  
  CONCLUSIONS
  Our study identified a strong association of rs2910164 of miR-146a with BD in a Chinese population and decreased expression of miR-146a and certain proinflammatory cytokines in individuals carrying the CC genotype.
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: Qingyun
authors.initials: Q
authors.lastname: Zhou
authors.forename: Shengping
authors.initials: S
authors.lastname: Hou
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Xinyu
authors.initials: X
authors.lastname: Li
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Tan
authors.forename: Lin
authors.initials: L
authors.lastname: Wei
authors.forename: Bo
authors.initials: B
authors.lastname: Lei
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*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics*; D014607:Uveomeningoencephalitic Syndrome / Q000235:genetics*; D055815:Young Adult
chemical_list: D016207:Cytokines; C494041:ETS1 protein, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D050784:Proto-Oncogene Protein c-ets-1