title: Coding sequence 1 and promoter single nucleotide polymorphisms in the CTLA-4 gene in Wegener's granulomatosis.
abstract: OBJECTIVE
  To analyze the association of Wegener's granulomatosis (WG) with 2 single nucleotide polymorphisms (SNP), a +49 A/G polymorphism in coding sequence (CDS) 1 and a C/T base exchange in the promoter region at position -318.
  
  
  METHODS
  Restriction enzyme digestion of PCR amplified genomic DNA was used to analyze the CTLA-4 SNP in 32 patients with WG and 100-122 ethnically matched healthy controls.
  
  
  RESULTS
  Patients were more often heterozygous for C/T in the promoter region (31% of the patients vs 14% of controls; p < 0.05). Homozygosity for C was less frequent in patients (69% of patients vs 86% of controls; p < 0.05). There was no association with the A/G SNP in CDS 1. There was a linkage disequilibrium between allele A of CDS 1 and the shortest allele, 86 bp, in the (AT)n of the 3' untranslated region in controls but not in patients.
  
  
  CONCLUSIONS
  The CTLA-4 SNP in the promoter region at position -318 is associated with WG. The loss of linkage disequilibrium between allele A of CDS 1 and the short 86 bp in the (AT)n in patients indicates that the promoter SNP and the (AT)n polymorphism are independent genetic risk factors.
authors.affiliation: Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Giscombe
authors.forename: Xiongbiao
authors.initials: X
authors.lastname: Wang
authors.forename: Deren
authors.initials: D
authors.lastname: Huang
authors.forename: Ann Kari
authors.initials: AK
authors.lastname: Lefvert
mesh_terms: D000069594:Abatacept; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014890:Granulomatosis with Polyangiitis / Q000453:epidemiology / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D018796:Immunoconjugates; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept