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Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY
Inés Urrutia1, Rosa Martínez1, Tamara López-Euba1
1BioCruces Health Research Institute, Cruces University Hospital, UPV-EHU, CIBERDEM, CIBERER, Barakaldo, Spain.
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.
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