title: Germline mutations in TGM2 do not contribute to coeliac disease susceptibility in the Swedish population.
abstract: OBJECTIVE
  Coeliac disease (CD) shows a strong genetic predisposition involving HLA-DQ2 and non-HLA components. Tissue transglutaminase, encoded by TGM2, occupies a central role in the CD pathogenesis, necessary for the deamidation of specific glutamine residues of alpha-gliadin creating a T-cell epitope that binds with increased affinity to DQ2. To investigate whether germline mutations in TGM2 contribute to disease susceptibility we have carried out a comprehensive analysis of the gene in 52 patients with CD.
  
  
  METHODS
  Blood samples were collected from 52 children with biopsy proven CD attending one Swedish centre. DNA was extracted from lymphocytes and all exons and intron-exon boundaries of the TGM2 gene and the alternatively spliced form of the gene were screened for mutations.
  
  
  METHODS
  Mutational analysis was undertaken by a combination of conformational specific gel electrophoresis and direct sequencing.
  
  
  RESULTS
  Three novel polymorphisms were identified but no pathogenic mutations were detected.
  
  
  CONCLUSIONS
  There is no evidence from this study that mutations in TGM2, which lead to an altered protein, contribute to CD susceptibility.
authors.affiliation: Institute for Cancer Research, Sutton, Surrey, UK. s.popat@icr.ac.uk
authors.forename: S
authors.initials: S
authors.lastname: Popat
authors.forename: L
authors.initials: L
authors.lastname: Hogberg
authors.forename: S
authors.initials: S
authors.lastname: McGuire
authors.forename: H
authors.initials: H
authors.lastname: Green
authors.forename: S
authors.initials: S
authors.lastname: Bevan
authors.forename: L
authors.initials: L
authors.lastname: Stenhammar
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000293:Adolescent; D002446:Celiac Disease / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D018095:Germ-Line Mutation; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011110:Polymorphism, Genetic; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D011503:Transglutaminases / Q000235:genetics*
chemical_list: D017931:DNA Primers; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins