DR4 and susceptibility to type I diabetes mellitus: discrimination of high risk and low risk DR4 haplotypes on the basis of TA10 typing.

DR4 related serological heterogeneity differences between type I diabetic and normal individuals previously observed appear to be due to differences in the DQ subregion. An Australasian sera study has identified two subsets of DQw3, the DQ allele in linkage disequilibrium with DR4, one of which (DQw3S) is present in 95.2% of diabetic DR4 compared with 58.1% of normal DR4 individuals (p less than 0.0005). The DQw3 subset showing a negative association with diabetes, DQw3L, appears to be closely related to or identical to TA10 a DQ subregion product previously described and studied in the 9th International Workshop. Analysis of the Workshop data showed a strong association of TA10- in type I diabetic DR4 individuals (93.5% v 69.1% in DR4 + normals) (p less than 0.0005). B44 appears to show an association with the presence of TA10 in DR4 positive individuals. This observation is suggestive of positive linkage disequilibrium and may explain the decreased frequency of the B44-DR4 haplotype in type I diabetes.