A T cell receptor beta chain polymorphism is associated with patients developing insulin-dependent diabetes after the age of 20 years

We have studied the BglII polymorphism near the T cell receptor beta chain constant region (TcR-Cβ) gene, HLA-DR genotypes and certain autoimmune features in 102 patients with type I (insulin-dependent) diabetes. There was a significant decrease in the frequency of the 1:1 genotype (P= 0.008) and an increase in the 1:2 genotype (P= 0.03) of the BglII TcR polymorphism in the group of patients who developed type-I diabetes after the age of 20 years. This group of patients also showed an increased incidence of autoantibodies (especially islet cell antibody), a family history of diabetes and the presence of other autoimmune diseases. The frequency of this polymorphism in patients who developed type I diabetes before the age of 20 years was similar to a non-diabetic group. These results suggest that there are two genetically distinct groups of patients with type I diabetes. HLA-DR3 and HLA-DR4 genotypes were also increased in the diabetic patients but no significant difference was observed between HLA-DR genotypes, the TcR-Cβ genotypes, the age of diagnosis or with other autoimmune features. Patients developing type I (insulin-dependent) diabetes after the age of 20 years have an additional genetic susceptibility for diabetes associated with the TcR-Cβ gene.