Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY

PLoS One. 2017 Jan 4;12(1):e0169389. doi: 10.1371/journal.pone.0169389. eCollection 2017.

Abstract

Objective: The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY.

Materials and methods: 160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY) were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4); 1 risk allele (DR3 or DR4); 2 risk alleles (DR3 and/or DR4).

Results: Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7-48.6) and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29-0.96) and OR 0.06 (95% CI: 0.02-0.18), respectively.

Conclusions: The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4) reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes.

MeSH terms

  • Alleles*
  • Case-Control Studies
  • Child
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency / genetics
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Male
  • Risk Factors
  • Spain

Substances

  • HLA-DRB1 Chains

Supplementary concepts

  • Mason-Type Diabetes

Grants and funding

This work was partially supported by grants from the University of the Basque Country, UPV/EHU (IT795-13), from the Department of Health of the Basque Government (GV2010111185) and from ISCIII (PI14/01104) integrated into the National R&D&I Plan 2013-2016 and co-financed by FEDER (European Funds for Regional Development). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.