HLA haplotype study of 53 juvenile insulin‐dependent diabetic (I.D.D.) families

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Abstract
Families (53) with at least one IDD [insulin-dependent diabetes] patient were genotyped for 5 markers of the HLA complex including Bf [properdin factor B] and DR. In 8 families one of the parents was also affected and in 12 families more than 2 children were diseased. In total, 76 patients were genotyped. Their haplotypes were compared with those of 106 unrelated controls (the parents of 53 genotyped families). Three haplotypes or segments of them (A2, Cw3, B15, BfS, DR4; Aw30, Cw5, B18, BfF1, DR3; and A1, Cw7, B8, BfS, DR3) were found more frequently in IDD patients. Measured by the .delta. formula, the association of the postulated IDD susceptibility gene was very strong with the D-end of 2 of these haplotypes: BfF1, DR3 and BfS, DR4. The association was weak with the DR3 of the haplotype A1, Cw7, B8, BfS, DR3. An excess of HLA-identical affected siblings was found. An excess of DR3/DR4 heterozygotes was observed. By contrast, the observed frequency of patients homozygous for DR3 or DR4 was not increased, but even slightly decreased. A model of inheritance is supported comprising at least 2 closely linked specifically diabetic loci (most of the time marked by B18, BfF1, DR3 and B15, BfS, DR4) and a non-specifically diabetic haplotype favoring auto-immunization (most of the time marked by B8, BfS, DR3). This model is discussed in the light of the presented data and of those of the literature.