Susceptibility to type I diabetes in women is associated with the CD3 epsilon locus on chromosome 11

SUMMARY Type I diabetes is associated with the DQ loci of the MHC and to a lesser extent with the T cell antigen receptor (TcR) beta chain genes. The non‐obese diabetic (NOD) mouse is an animal model of human diabetes, in which up to 90% of female mice develop overt insulin‐dependent diabetes. Genetic studies in the NOD mouse suggest that there are at least three diabetogenic genes; one that maps to the MHC, another that may map to the mouse Thy‐I locus, and a third that has still to be identified. We have investigated loci in the vicinity of the human Thy‐I locus on chromosome 1 Iq23 and report here the results of restriction fragment length polymorphism (RFLP) analysis of the CD3 epsilon locus of 168 Caucasoid patients with type I diabetes. While no association was found between this locus and type I diabetes, a significant difference in the frequency of the CD3 epsilon 8‐kb allelc was found between male and female patients (0.268 versus 0.430; p < 0.0025, Pc= 002) and between female patients and healthy female controls (0.430 versus 0.267; P < 0.015). These results suggest that a gene residing on chromosome 1 Iq23 may confer susceptibility to type 1 diabetes in women.