title: Analysis of the CTLA4 gene in Swedish coeliac disease patients.
abstract: BACKGROUND
  A genetic susceptibility to coeliac disease is well established, involving HLA and non-HLA components. CTLA4 is an important regulator of T-cell function and some studies have suggested that sequence variation in the gene might be a determinant of disease susceptibility, although the evidence is conflicting.
  
  
  METHODS
  Sixty-two children with biopsy-proven coeliac disease attending a single centre in Sweden were studied. All were genotyped for presence of the HLA-DQA1*0501, B 1*0201 alleles. Those who carried the HLA-DQ heterodimer (58/62) were genotyped for the +49 (A/G) exon I polymorphism. The transmission disequilibrium test (TDT) was used to test for association between coeliac disease and the A allele. The entire CTLA4 gene was screened for other sequence variants using a combination of conformation-sensitive gel electrophoresis and direct sequencing.
  
  
  RESULTS
  A significant association between the exon I polymorphism and coeliac disease was observed (P = 0.02). No other sequence variants in CTLA4 were detected.
  
  
  CONCLUSIONS
  This study provides further evidence that variation in CTLA4 is a determinant of coeliac disease susceptibility. If not mediated through the +49 (A/G) dimorphism directly, then the effect is likely to be mediated through linkage disequilibrium.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Surrey, UK. sanjay@icr.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Popat
authors.forename: N
authors.initials: N
authors.lastname: Hearle
authors.forename: J
authors.initials: J
authors.lastname: Wixey
authors.forename: L
authors.initials: L
authors.lastname: Hogberg
authors.forename: S
authors.initials: S
authors.lastname: Bevan
authors.forename: W
authors.initials: W
authors.lastname: Lim
authors.forename: L
authors.initials: L
authors.lastname: Stenhammar
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D002446:Celiac Disease / Q000235:genetics*; D002648:Child; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D018796:Immunoconjugates; D015810:Linkage Disequilibrium / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D013548:Sweden
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D018796:Immunoconjugates; D000069594:Abatacept