Genetic screening for individuals at high risk for type 1 diabetes in the general population using HLA class ll alleles as disease markers. A comparison between three European populations with variable rates of disease incidence

Robert Hermann, S. C. Bartsocas, Gy Soltész, A. Vazeou, P. Paschou, E. Bozas, A. Malamitsi-Puchner, O. Simell, M. Knip, J. Ilonen

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Background. To develop screening strategies for identification of individuals at increased genetic risk for type 1 diabetes in three populations with variable disease incidence rates and distinct ethnic of origin. Methods. A stepwise HLA DQB1-DQA1-DRB1-based screening approach was evaluated. Patients with childhood-onset type 1 diabetes were recruited from Finland (n = 1739), Hungary (n = 149), and Greece (n = 119). Consecutive newborns (2568 from Finland and 1047 from Greece) or healthy schoolchildren (n = 177 from Hungary) served as controls. Results. The DQB1*02/0302 genotype conferred the highest disease risk in all populations. The DQB1*02/y (y ≠ DQB1* 0301,*0302,*0602,*0603, *0604) genotypes were more common and conferred a higher disease risk in the Greek population (OR 4.9) compared to the Finns (OR 1.2). DQB1*0302/x (x ≠ DQB1*02, *0301, *0602, *0603, *0604) genotypes were, in contrast, more prevalent among Finnish cases (32.7%) as compared to Hungarians (18.1%) or Greeks (13.5%). The protective DQB1*0602 or *0603 positive genotypes were most common in the Finns, while DQB1*0301 was more common in Hungarians and Greeks. In a groups, DQA1 and DRB1*04 typing considerably increased the sensitivity of the DQB1-based screening. The different high-risk genotype combinations present in about 10% of the background population had a diagnostic sensitivity of 60% in Finland and 80% in Hungary and Greece. Conclusions. HLA DR-DQ-based screening is a feasible tool for the identification of individuals at increased genetic risk for type 1 diabetes in populations with diverse genetic background. The risk markers should, however, be individually selected for the target population since the screening efficiency of various markers is highly dependent on the ethnic group studied.

Original languageEnglish
Pages (from-to)322-329
Number of pages8
JournalDiabetes/Metabolism Research and Reviews
Issue number4
Publication statusPublished - Jul 1 2004



  • Genetic screening
  • Genetic susceptibility
  • HLA DQ
  • Incidence
  • Type 1 diabetes mellitus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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