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

doi:10.2337/diacare.19.8.795

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

Jorma Ilonen, MD,
Helena Reijonen, PHD,
Elja Herva, MD,
Minna Sjöroos, MSC,
Antti Iitiä, PHD,
Timo Lövgren, PHD,
Riitta Veijola, MD,
Mikael Knip, MD,
Hans K Åkerblom, MD and
The Childhood Diabetes in Finland (DIME) Study Group

Turku Immunology Center and Department of Virology, University of Turku Turku
National Public Health Institute Oulu
Department of Biotechnology, University of Turku Turku
Department of Pediatrics, University of Oulu Oulu
Second Department of Pediatrics, Children's Hospital, University of Helsinki Helsinki, Finland

Address correspondence and reprint requests to Jorma Ilonen, MD, Department of Virology, University of Turku, Kiinamyllynkatu 13, FIN-20520 Turku, Finland. E-mail: jorma.ilonen{at}utu.fi

Abstract

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 screening 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.