The HLA-DR genotypes of 158 new type I diabetic probands from simplex families are compared with those of 43 multiply affected sibships. There were no significant differences in the gene frequencies of the insulindependent diabetes mellitus (IDDM)-associated alleles, DR3 and DR4, and whereas the DR3/4 heterozygotes were as frequent among simplex probands as among the first affected of multiplex sibships, subsequently affected sibs displayed lower frequencies of this genotype in this as well as in previously reported samples, indicating that the excessive risk associated with DR3/ 4 heterozygosity depends on the order of affection and thus on environmental factors. It is proposed that the penetrance of the susceptibility gene is enhanced by epistatic effects of this genotype and that this enhancement is strongest under conditions of low environmental liability. Thus, the excessive risk for DR3/4 individuals appears to depend on secondary interactions between DR and the environmental factors that trigger the onset of this disease and does not in itself indicate the existence of distinct susceptibility alleles in coupling with these genes, i.e., of genetic heterogeneity or overdominance.
Skip Nav Destination
Original Contributions| September 01 1986
Excess of DR3/4 in Type I Diabetes: What Does It Portend?
Address reprint requests to Pablo Rubinstein, MD, Immunogenetics, The New York Blood Center, 310 East 67th Street, New York, 10021
- Views Icon Views
- Share Icon Share
P Rubinstein, M Walker, F Ginsberg-Fellner; Excess of DR3/4 in Type I Diabetes: What Does It Portend?. Diabetes 1 September 1986; 35 (9): 985–989. https://doi.org/10.2337/diab.35.9.985
Download citation file: