T cell receptor gamma gene polymorphisms and class II human lymphocyte antigen genotypes in patients with celiac disease from the West of Ireland

Although celiac disease has one of the strongest human lymphocyte antigen (HLA) class II associations of any human illness, it is clear that at least one gene that is not linked to the HLA region also is required for its pathogenesis. The occurrence of large numbers of T cells in the bowel mucosa of patients and the recent description of T cell receptor (TCR) chain polymorphic variants identified by restriction fragment length polymorphism analysis led the authors to examine TCRγ genotypes in relation to HLA-DR, DQ genotypes in 89 patients with celiac disease and 55 control subjects from the West of Ireland. The overall frequency of TCRγ genotypes in patients and control subjects was comparable. However, most of the patients had 1 of 3 HLA-DR3 genotypes (DR3/15, 3/7, or 3/3), and there was a significant alteration of the expected frequency of TCRγ genotypes among patients with these three genotypes. The major differences were an increased association of HLA-DR3 homozygosity, with TCRγ genotypes having a 16.0 kb fragment and an increased frequency of DR3/7 heterozygosity and decreased frequency of DR3/15 heterozygosity, respectively, in association with the TCRγ 13.0/11.3 kb genotype. Based on their results, there is the possibility that an interaction between the products of two polymorphic and unlinked gene regions contributes to the pathogenesis of celiac disease.