TcR-alpha and TcR-beta dialellic RFLPs in insulin-dependent (type I) Caucasian diabetic patients

We studied the association of a T-cell receptor (TcR) beta restriction fragment length polymorphism (RFLP) and a new TcR-alpha RFLP with insulin-dependent (Type I) diabetes mellitus. This study is part of our effort to find new non-HLA disease genes involved in this chronic organ-specific autoimmune disease. Distribution of a 9.2 kb and a 10.0 kb diallelic TcR beta 2 RFLP was not different in diabetics and controls. A new TcR-alpha RFLP, which gave a 2.7 kb Hind III restriction fragment (A2 allele) was found with a frequency of 0.78 in a population of 78 IDDM patients, compared to 0.68 in 68 control subjects (X2 = 3.62, p = 0.057). In 11 multiplex families studied, a high prevalence of the A2 allele was also observed, but cosegregation with the disease was not seen. Our data suggest that a TcR beta 2 RFLP is not associated with the disease, whereas a particular T-cell receptor alpha germline RFLP (A2 allele) is increased in Type I diabetics although formal proof of linkage is lacking. HLA typing reconfirmed that the HLA-DR4 specificity and the DQ allele HLA-DQw8 are primary risk markers in insulin-dependent (Type I) diabetes mellitus.