ROLE OF T-CELL RECEPTOR DELTA-GENE IN SUSCEPTIBILITY TO CELIAC-DISEASE

There is a strong genetic influence on the susceptibility to celiac di sease. Although in the vast majority of patients with celiac disease, the HLA-DQ(alpha 10501, beta 1*0201) heterodimer encoded by the allel es HLA-DQA10501 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 me diated immune response could potentially influence susceptibility to c eliac disease. The density of T cells using the gamma delta T cell rec eptor (TCR) is considerably increased in the jejunal epithelium of pat ients with celiac disease, an abnormality considered to be specific fo r celiac disease. This suggests an involvement of gamma delta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease susceptibility we carried o ut an association study and genetic linkage analysis using a highly po lymorphic microsatellite marker at the TCRD locus on chromosome 14q11. 2. The association study demonstrated no significant difference in all ele frequencies of the TCRD gene marker between celiac disease patient s and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, perfo rmed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac disease versus the TCRD gene marker excluded linkage, sugg esting that there is no determinant contributing to celiac disease sta tus at or 5 cM distant to the analyzed TCRD gene marker. In conclusion , the results of the present study provide no evidence that the analyz ed TCRD gene contributes substantially to celiac disease susceptibilit y.