Abstract
ObjectiveThe 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 Methods160 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).ResultsCompared 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.ConclusionsThe 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.
Highlights
Diabetes mellitus represents a group of metabolic disorders characterized by increased levels of blood glucose resulting from defects in insulin secretion, insulin action, or both.Type 1 diabetes mellitus develops primarily in youth as a result of autoimmune destruction of the pancreatic beta-cells and is characterized by absolute insulin deficiency
Compared with type 1 diabetes, patients with Maturity-onset diabetes of the young (MODY) carried higher frequency of 0 risk alleles, OR 22.7 and lower frequency of 1 or 2 risk alleles, OR 0.53 and OR 0.06, respectively
The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY
Summary
Type 1 diabetes mellitus develops primarily in youth as a result of autoimmune destruction of the pancreatic beta-cells and is characterized by absolute insulin deficiency. In this disorder, glutamic acid decarboxylase (GADA), tyrosine phosphatase (IA2A), zinc transporter 8 (ZnT8A) and insulin autoantibodies (IAA) are currently recognized as autoimmune process markers [1, 2]. The first genetic contribution strongly associated with type 1 diabetes was found within the HLA region on chromosome 6p21. Susceptibility to, and protection against development of autoimmune diabetes are associated with the highly polymorphic sequences of the HLA class II genes. The strongest susceptibility haplotypes described are HLA DRB1Ã03-DQA1Ã0501-DQB1Ã0201 and HLA DRB1Ã04-DQA1Ã0301-DQB1Ã0302 especially when both are present in the genotype. [3]
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