title: Mutational analysis of CD28 in coeliac disease.
abstract: BACKGROUND
  Coeliac disease shows a strong genetic predisposition involving HLA-DQ2 and non-HLA components. The CD28 cell surface molecule, encoded by CD28, represents a potential candidate coeliac disease susceptibility gene. Furthermore, some studies have demonstrated linkage to the CD28/CTLA4 gene region. To investigate whether germline mutations in CD28 contribute to coeliac disease susceptibility, we have carried out a comprehensive analysis of the gene in Swedish patients with biopsy-proven disease.
  
  
  METHODS
  Blood samples were collected from 52 children with biopsy proven coeliac disease attending one Swedish centre. DNA was extracted from lymphocytes and all exons and intron-exon boundaries of CD28 were screened for mutations. Analysis of CD28 was undertaken by a combination of conformation specific gel electrophoresis and direct sequencing.
  
  
  RESULTS
  Three sequence variants were identified: a synonymous G-->4A substitution at position 3 of codon 35 encoding alanine, a synonymous G-->A substitution at position 3 of codon 70 encoding glycine, and a T-->C substitution at nucleotide +17 of intron 3. No pathogenic variants were detected.
  
  
  CONCLUSIONS
  There is no evidence from this study that mutations in CD28, which lead to an altered protein, contribute to coeliac disease susceptibility.
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: S
authors.initials: S
authors.lastname: Bevan
authors.forename: L
authors.initials: L
authors.lastname: Hogberg
authors.forename: L
authors.initials: L
authors.lastname: Stenhammar
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000293:Adolescent; D018106:CD28 Antigens / Q000235:genetics*; D002446:Celiac Disease / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D013548:Sweden
chemical_list: D018106:CD28 Antigens