title: A candidate gene approach to ANCA-associated vasculitis reveals links to the C3 and CTLA-4 genes but not to the IL1-Ra and Fcγ-RIIa genes.
abstract: OBJECTIVE
  The aim of the study is to search for associations between Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and polymorphisms in the genes of four key molecules possibly involved in different pathogenic pathways; complement C3, CTLA-4, Fcγ-RIIa and IL1-Ra.
  
  
  METHODS
  Patients with AAV (n=105) subgrouped as microscopic polyangiitis or granulomatosis with polyangiitis (Wegener's granulomatosis) and myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA positive were compared to a control group of 200 blood donors. Polymorphisms in the genes were analysed with PCR amplification of DNA.
  
  
  RESULTS
  The diagnosis of AAV was confirmed in the 105 cases. The gene frequency of C3F was 0.27 in the PR3-ANCA subgroup (p=0.041) compared to 0,19 in the control group. The number of patients homozygous for the shortest 86 bp allele of CTLA-4 was significantly decreased in the whole group of patients (p=0.049). No differences were evident in the Fcγ-RIIa and IL1-Ra polymorphisms when compared to controls, neither in the whole group of patients, nor in any of the sub-groups.
  
  
  CONCLUSIONS
  The aberrant gene frequency of the C3F allele among PR3-ANCA positive patients and the findings with the CTLA-4 polymorphism indicates that complement may be involved in pathogenesis and that T-cell activation also is of importance in these diseases.
authors.affiliation: Departments of Nephrology, Lund University, Lund, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Persson
authors.forename: Birgitta
authors.initials: B
authors.lastname: Gullstrand
authors.forename: Asa
authors.initials: A
authors.lastname: Pettersson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sturfelt
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Mårten
authors.initials: M
authors.lastname: Segelmark
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000175:diagnosis / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D015331:Cohort Studies; D003176:Complement C3 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D008040:Genetic Linkage / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D008297:Male; D011446:Prospective Studies; D017452:Receptors, IgG / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D060908:CTLA-4 Antigen; D003176:Complement C3; C080568:Fc gamma receptor IIA; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017452:Receptors, IgG