Rapid HLA-DQB1 Genotyping for Four Alleles in the Assessment of Risk for IDDM in the Finnish Population


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Abstract

OBJECTIVETo 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 *03020 and *0201) and protection from it (DQB1 *0602/*0603 and *0301).RESEARCH DESIGN AND METHODSA 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 screening purposes. The method utilizes time-resolved fluorometry to detect the hybridization of lanthanide-labeled allele-specific oligonucleotide probes with amplified gene product.RESULTSA total of 61.9 percent 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 percent of the reference population. In patients and control subjects, the frequencies of low risk genotypes were 28.0 and 22.1 percent, respectively, and those of decreased risk genotypes, 10.0 and 63.6 percent. The relative risk of a *0201/*0302 genotype was 53.5 (31.1-92.8) compared with the decreased risk genotypes (63.6 percent of controls). The graded risk estimation was equally efficient in assessing the risk of IDDM in sibling of child with IDDM.CONCLUSIONThe near-automatic typing procedure developed is attractive for large-scale screening projects, such as diabetes prevention and intervention trials.

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