No allelic variation in genes with high gliadin homology in patients with celiac disease and type 1 diabetes.
Celiac disease (CD) is a complex inflammatory disorder of the small intestine, induced by dietary gluten in genetically susceptible individuals. CD is strongly associated with HLA-DQ2 and it has recently been established that gut-derived DQ2-restricted T cells from patients with CD predominantly recognize gluten-derived peptides in which specific glutamine residues are deamidated to glutamic acid by tissue transglutaminase. Recently, intestinally expressed human genes with high homology to DQ2-gliadin celiac T-cell epitopes have been identified. Single or double point mutations which would increase the celiac T-cell epitope homology, and mutation in these genes, leading to the expression of glutamic acid at particular positions, could hypothetically be involved in the initiation of CD in HLA-DQ2-positive children. Six gene regions with high celiac T-cell epitope homology were investigated for single-nucleotide polymorphisms using direct sequencing of DNA from 20 CD patients, 27 type 1 diabetes mellitus (T1DM) patients with associated CD, 24 patients with T1DM without CD and 110 healthy controls, all of Caucasian origin. No variants in any of these genes in any of the investigated groups were found. We conclude that gut-expressed human celiac epitope homologous peptides are unlikely to represent non-HLA risk factors in the development of celiac disease in Caucasians.
Department of Clinical Immunology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense, Denmark.
Christian
C
Nielsen
Dorte
D
Hansen
Steffen
S
Husby
Bendt Brock
BB
Jacobsen
Søren T
ST
Lillevang
D002446:Celiac Disease / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005903:Gliadin / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics; D006801:Humans
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D005903:Gliadin