The Bf system in diabetes-gene interaction or linkage disequilibrium?

HLA and Bf genotypes have been determined in 75 Type 1 (insulin-dependent) diabetic probands ascertained from two family studies. The Bf associations were similar in those families with two affected children compared with those families with one affected child. The strong association of B18 with the rare allele BfF1 was confirmed but, with rare exception, the gene encoding for BfF1 only occurred on chromosomes coding for both B18 and CW5. These findings are similar to the strong allelic association between these specificities found more frequently in Southern Europe and Spain, but no HLA-A locus association was found in the present study. All HLA-B 8 positive subjects and 15 out of 16 BW62 positive probands possessed BfS. In contrast to other reports, we could not find any evidence to support the idea that BfF1 is associated with a younger age of onset of diabetes. It is concluded that there is no specific susceptibility gene for Type 1 diabetes linked to the Bf locus and that the Bf associations can be explained purely on the basis of the known allelic association, or linkage disequilibrium, within the HLA system.