Rapid HLA-DQB1 genotyping for four alleles in the assessment of risk for IDDM in the Finnish population

OBJECTIVE - To study the effectiveness of MHC genotyping in the assessment of risk for IDDM based on the identification of alleles that are significantly associated with risk for IDDM (DQB1*0302 and *0201) and protection from it (DQB1*0602/*0603 and *0301). RESEARCH DESIGN AND METHODS - A long series of 649 index cases of IDDM, together with their healthy siblings and 756 healthy blood donors, was collected in Finland. The samples were analyzed using a large-scale assay procedure that was developed for rapid screen ing purposes. The method utilizes time-resolved fluorometry to detect the hybridization of lanthanide-labeled allele-specific oligonucleotide probes with amplified gene product. RESULTS - A total of 61.9% of IDDM index cases had high risk (DQB1*0201/*0302) or moderate risk (DQB1*0302/x [x meaning DQB1*0302 or a nondefined allele]) genotypes compared with 14.3% of the reference population. In patients and control subjects, the frequencies of low risk genotypes were 28.0 and 22.1%, respectively, and those of decreased risk genotypes, 10.0 and 63.6%. The relative risk of a *0201/*0302 genotype was 53.5 (31.1-92.8) compared with the decreased risk genotypes (63.6% of controls). The graded risk estimation was equally efficient in assessing the risk of IDDM in siblings of child with IDDM. CONCLUSION - The near-automatic typing procedure developed is attractive for large scale screening projects, such as diabetes prevention and intervention trials.