There is a strong genetic influence on the susceptibility to
celiac disease. Although in the vast majority of patients with
celiac disease, the
HLA-DQ(alpha1*0501, beta1*0201) heterodimer encoded by the alleles
HLA-DQA1*0501 and
HLA-DQB1*0201 seems to confer the primary
disease susceptibility, it cannot be excluded that other genes contribute to
disease susceptibility, as indicated by the difference in concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%). Obviously other genes involved in the genetic control of T cell mediated immune response could potentially influence susceptibility to
celiac disease. The density of T cells using the gammadelta
T cell receptor (TCR) is considerably increased in the jejunal epithelium of patients with
celiac disease, an abnormality considered to be specific for
celiac disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to
celiac disease susceptibility we carried out an association study and genetic linkage analysis using a highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The association study demonstrated no significant difference in allele frequencies of the TCRD gene marker between
celiac disease patients and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, performed in 23 families, the logarithm of the odds (LOD) scores calculated for
celiac disease versus the TCRD gene marker excluded linkage, suggesting that there is no determinant contributing to
celiac disease status at or 5 cM distant to the analyzed TCRD gene marker. In conclusion, the results of the present study provide no evidence that the analyzed TCRD gene contributes substantially to
celiac disease susceptibility.