title: A functional variant of PTPN22 confers risk for Vogt-Koyanagi-Harada syndrome but not for ankylosing spondylitis.
abstract: BACKGROUND
  Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a key negative regulator of T lymphocytes and has emerged as an important candidate susceptibility factor for a number of immune-related diseases. This study aimed to examine the predisposition of PTPN22 SNPs to Vogt-Koyanagi-Harada (VKH) syndrome and acute anterior uveitis (AAU) associated with ankylosing spondylitis (AS).
  
  
  METHODS
  A total of 1005 VKH syndrome, 302 AAU+AS+ patients and 2010 normal controls among the Chinese Han population were enrolled in the study. Genotyping, PTPN22 expression, cell proliferation, cytokine production and cell activation were examined by PCR-RFLP, Real-time PCR, CCK8, ELISA and Flow cytometry.
  
  
  RESULTS
  The results showed significantly increased frequencies of the rs2488457 CC genotype and C allele but a decreased frequency of the GG genotype in VKH syndrome patients (PBonferroni correction (Pc) = 3.47×10(-7), OR = 1.54; Pc = 3.83×10(-8), OR = 1.40; Pc = 6.35×10(-4), OR = 0.62; respectively). No significant association of the tested SNPs with AAU+AS+ patients was observed. Functional studies showed a decreased PTPN22 expression, impaired cell proliferation and lower production of IL-10 in rs2488457 CC cases compared to GG cases (Pc = 0.009, Pc = 0.015 and Pc = 0.048 respectively). No significant association was observed concerning T cell activation and rs2488457 genotype.
  
  
  CONCLUSIONS
  The study showed that a functional variant of PTPN22 confers risk for VKH syndrome but not for AAU+AS+ in a Chinese Han population, which may be due to a modulation of the PTPN22 expression, PBMC proliferation and IL-10 production.
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qi
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Shengping
authors.initials: S
authors.lastname: Hou
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Du
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Hongsong
authors.initials: H
authors.lastname: Yu
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Cao
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liao
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 Key Laboratory of Ophthalmology and Chongqing Eye Institute, Chongqing, P. R. China.
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008297:Male; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000201:enzymology* / Q000235:genetics*; D014607:Uveomeningoencephalitic Syndrome / Q000097:blood / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22