title: CT60 and +49 polymorphisms of CTLA 4 are associated with ANCA-positive small vessel vasculitis.
abstract: OBJECTIVE
  To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel vasculitis (SVV).
  
  
  METHODS
  The CTLA-4 CT60 (exon 4), +49 (exon 1) and -318 (promoter region) genotypes were determined by PCR and restriction fragment length polymorphism (RFLP) in 222 white Caucasians of UK origin with SVV and 670 ethnically matched controls.
  
  
  RESULTS
  The CTLA-4 exon 1 (+49) and 4 (CT60) polymorphisms are associated with SVV (+49: chi(2) = 10.965, P = 0.004; CT60: chi(2) = 12.017, P = 0.002). Both disease-susceptible and disease-protective haplotypes have been identified in this cohort, and their frequencies are similar in the subtypes of WG and microscopic polyangiitis.
  
  
  CONCLUSIONS
  This study provides further evidence that CTLA-4, a susceptibility locus for a number of common autoimmune diseases, may also be involved in the development of ANCA-associated SVV.
authors.affiliation: Renal Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Kamesh
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Heward
authors.forename: Julie M
authors.initials: JM
authors.lastname: Williams
authors.forename: Stephen C L
authors.initials: SC
authors.lastname: Gough
authors.forename: Konstantia-Maria
authors.initials: KM
authors.lastname: Chavele
authors.forename: Alan
authors.initials: A
authors.lastname: Salama
authors.forename: Charles
authors.initials: C
authors.lastname: Pusey
authors.forename: Caroline O S
authors.initials: CO
authors.lastname: Savage
authors.forename: Lorraine
authors.initials: L
authors.lastname: Harper
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000235:genetics* / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human