ASSESSMENT OF THE DQB1-DQA1 COMPLETE GENOTYPE ALLOWS BEST PREDICTION FOR IDDM

OBJECTIVE- To analyze the HLA-DQ (human leukocyte antigen) genetic ass ociation with insulin-dependent diabetes mellitus (IDDM) patients of t he Northeast Italian population. RESEARCH DESIGN AND METHODS- Fifty-on e IDDM patients and 52 healthy control subjects were molecularly typed for DQB1 and DQA1 loci by using allele-specific oligonucleotide probe s and polymerase chain reaction amplified genomic DNA. DNA enzyme immu noassay was used to assess allele specificities. RESULTS- IDDM status strongly correlated with DQB1 alleles carrying a nonaspartic acid (non -Asp) residue in position 57 of DQ beta-chain and DQA1 alleles with an arginine (Arg) residue in position 52 of DQ alpha-chain. Individuals with two DQB1(non-Asp) alleles and two DQA1(Arg) alleles had the highe st relative risk for disease: they constituted similar to 40% of IDDM patients compared with 0% of control subjects. Heterozygosis at either residue 57 of DQB1 or residue 52 of DQA1 was sufficient to abrogate s tatistical significance for disease association, although 47% of IDDM patients were included in these two groups compared with 21% of normal control subjects. On the other hand, the presence of two DQB1 alleles with Asp in position 57 was sufficient to confer resistance to diseas e irrespective of the DQA1 genotype. CONCLUSIONS- The results demonstr ate that the complete HLA-DQ genotype, more than a single DQB1 or DQA1 locus, should be determined to estimate the highest risk for disease. Screening a population for preventive purposes and/or early signs of IDDM should then take advantage of this result, and ''susceptible homo zygous'' individuals should be followed very closely and considered th e first group of choice for possible new therapeutic trials.