title: High C4 gene copy numbers protects against Vogt-Koyanagi-Harada syndrome in Chinese Han.
abstract: OBJECTIVE
  Considering the phenotypical consequences and association of C4 copy number variation (CNV) with various autoimmune diseases, we aimed to examine C4 CNVs for 1027 patients with Vogt-Koyanagi-Harada (VKH) syndrome and 2083 controls.
  
  
  METHODS
  C4 CNVs were examined by real-time PCR for 1027 patients with VKH and 2083 controls. Peripheral blood mononuclear cells (PBMC) were prepared from venous blood by Ficoll-Hypaque density-gradient centrifugation for cell culture. Cytokine production was examined by ELISA.
  
  
  RESULTS
  The expression of total C4 in serum was significantly decreased in patients with VKH as compared with controls (p=0.0010). A significant positive association between C4 expression with C4 CNVs was found (p=0.0023, r(2)=0.92). CNV analysis identified significantly decreased frequencies of more than two copies of C4A or more than four copies of total C4 in patients with VKH (Pc=1.42×10(-3) to 3.56×10(-4), OR=0.67 to 0.70). Linkage analysis showed the independent association of C4 with VKH syndrome from human leucocyte antigen (HLA)-DR4. No significant association was observed concerning type 1 T helper cell (Th1) cytokines and Th17 cytokine production by stimulated PBMCs and C4A copy number.
  
  
  CONCLUSIONS
  Our findings indicate a decreased expression of serum C4 and a decreased frequency of high C4 gene copy number in patients with VKH.
  
  
  BACKGROUND
  Chinese Clinical Trial Registration Number: ChiCTR-CCC-12002184.
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Chongqing Key Laboratory of Ophthalmology, Chongqing, China Chongqing Eye Institute, Chongqing, China.
authors.forename: Shengping
authors.initials: S
authors.lastname: Hou
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Chongqing Key Laboratory of Ophthalmology, Chongqing, China Chongqing Eye Institute, Chongqing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qi
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Chongqing Key Laboratory of Ophthalmology, Chongqing, China Chongqing Eye Institute, Chongqing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liao
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Chongqing Key Laboratory of Ophthalmology, Chongqing, China Chongqing Eye Institute, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Chongqing Key Laboratory of Ophthalmology, Chongqing, China Chongqing Eye Institute, Chongqing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: University Eye Clinic Maastricht, Maastricht, The Netherlands.
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Chongqing Key Laboratory of Ophthalmology, Chongqing, China Chongqing Eye Institute, Chongqing, China.
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D003181:Complement C4 / Q000235:genetics* / Q000378:metabolism; D056915:DNA Copy Number Variations / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D014607:Uveomeningoencephalitic Syndrome / Q000097:blood / Q000235:genetics* / Q000517:prevention & control*
chemical_list: D003181:Complement C4
keywords: Immunology; Inflammation