Population-based genetic screening for the estimation of Type 1 diabetes mellitus risk in Finland: selective genotyping of markers in the HLA-DQB1, HLA-DQA1 and HLA-DRB1 loci

S Nejentsev, M Sjöroos, T Soukka, M Knip, O Simell, T Lövgren, J Ilonen

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133 Citations (Scopus)


AIMS: To improve sensitivity and specificity of the diabetes risk assessment of the population-based genetic screening used in the Finnish Diabetes Prediction and Prevention (DIPP) trial.

METHODS: One thousand consecutive newborns enrolled in the DIPP were compared with 316 samples from children with Type 1 diabetes mellitus. A modification of the previously described technique based on hybridization of relevant PCR products with five lanthanide-labelled probes detected by time-resolved fluorometry (TRF) was used. A new probe was designed and allowed discrimination between DQB1*0602 and 0603 alleles, in addition to DQB1*02, *0301 or *0302, each of which required specific probes. A new, added screening strategy was developed for individuals carrying low-risk genotypes through specific typing of DQA1 *05 and *0201 alleles in DQB1*02 positive, and DRB1 typing for DR4 subtypes in DQB1*0302 positive subjects, with a new specifically designed high-resolution TRF-based DR4 subtyping technique.

RESULTS: This two-step screening approach enhanced the sensitivity of the detection of genetic risk for Type 1 diabetes mellitus in this cohort up to 85.4%. In the general population cohort, 24.4% were identified for prospective follow-up, 2.6% of these are expected to develop Type 1 diabetes mellitus before the age of 15 years. Exclusive typing for HLA-DQB1 locus as an alternative screening strategy had sensitivities of 26.3-77.2% with general population cohorts of 2.3-23.1% identified for follow-up.

CONCLUSIONS: The described strategy for genetic prediction of Type 1 diabetes mellitus relies on the convenient genotyping procedure and could be applied in large scale screening projects such as DIPP.

Original languageEnglish
Pages (from-to)985-92
Number of pages8
JournalDiabetic medicine
Issue number12
Publication statusPublished - Dec 1999
Externally publishedYes


  • Biomarkers
  • Child
  • Cohort Studies
  • DNA Probes
  • Diabetes Mellitus, Type 1/genetics
  • Finland
  • Genetic Testing
  • Genotype
  • HLA-DQ Antigens/genetics
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DR Antigens/genetics
  • HLA-DRB1 Chains
  • Humans
  • Infant, Newborn
  • Nucleic Acid Hybridization
  • Polymerase Chain Reaction
  • Prospective Studies
  • Risk Factors
  • Sensitivity and Specificity

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