Susceptibility to type I diabetes in women is associated with the CD3 epsilon locus on chromosome 11.
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 11q23 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 allele was found between male and female patients (0.268 versus 0.430; P less than 0.0025, Pc = 0.02) and between female patients and healthy female controls (0.430 versus 0.267; P less than 0.015). These results suggest that a gene residing on chromosome 11q23 may confer susceptibility to type I diabetes in women.
Wong
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Department of Medicine, King's College School of Medicine and Dentistry, London, England.
Moore
S
S
Orisio
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Millward
A
A
Demaine
A G
AG
D000328:Adult; D000483:Alleles; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D015342:DNA Probes; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization; D012150:Polymorphism, Restriction Fragment Length; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*
D015342:DNA Probes; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell; C061836:antigen T cell receptor, epsilon chain