Germline mutations in TGM2 do not contribute to coeliac disease susceptibility in the Swedish population

Germline mutations in TGM2 do not contribute to coeliac disease susceptibility in the Swedish population. 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. Design 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.