HLA genotype studies in juvenile insulin-dependent diabetes.
HLA genotypes were ascertained in 53 French Caucasian families, comprising 68 juvenile onset insulin-dependent diabetic siblings. Among the 49 alleles detected at different loci in the HLA complex (A, C, B, Bf, DR) 4 appeared to occur at a significantly higher frequency among the 53 index cases than in a control series of 116 healthy individuals: HLA-B18 (p < 10(-3)), DRw3, DRw4 and BfF1 (p < 10(-6)). The excess of HLA identical affected siblings confirms genotype disequilibrium and supports the hypothesis of an HLA-linked gene(s) conferring susceptibility. There was no increase of homozygosity for HLA DRw3 and DRw4 whereas there was a marked excess heterozygosity for HLA DRw3/DRw4 in diabetic patients (32% versus 0% in the control series, p < 0.001). These data provide evidence for the existence of two cooperating genes, linked to each of the HLA DR alleles.
D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D006680:HLA Antigens / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D011995:Recombination, Genetic
D006680:HLA Antigens