HLA-DQ screening for risk assessment of insulin dependent diabetes in northern Italy.

Genetic markers may be used to improve the prediction of insulin-dependent diabetes mellitus (type 1) in individuals with islet autoantibodies. In order to develop a risk assessment strategy for the Lombardy region of northern Italy based on genetic and immunological markers, we analyzed HLA DQA1 and DQB1 alleles in 60 type 1 probands and their first-degree relatives and 65 unrelated control subjects from the same area using polymerase chain reaction (PCR) and oligonucleotide probes. The major risk haplotypes were DQA1 0501-DQB10201 (39.1% of diabetic vs. 8.9% of non-diabetic haplotypes) and DQA1 0301-DQB10302(20% of diabetic vs 7.1% of non-diabetic haplotypes). Stratified analysis showed DQA10102-DQB10502 also to be associated with type 1 susceptibility when found together with DQA10501-DQB10201 or DQA10301-DQB10302. One type 1 patient had the type 1-protective DQA10102-DQB10602 haplotype. Overall, 88% of patients and 20% of unrelated control subjects had either DQA10501-DQB10201 or DQA10301-DQB10302 in the absence of DQA10102-DQB10602. These data suggest that typing for markers identifying these three haplotypes in the Lombardy population will achieve a sensitivity of almost 90% and exclude 80% of children from subsequent islet autoantibody testing.