Endocrine Abstracts

Background and Aim: Type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from the complex interaction among multiple genes, environmental factors and the immune system. Genome-wide association studies identified ERBB3 (Erb-b2 receptor tyrosine kinase 3) gene as a main susceptibility locus for T1DM. This gene encodes a member of the family of intracellular receptors of protein tyrosine kinases, which activates multiple signaling pathways including PI3K-Akt and MAPK; thus, regulating cell survival and proliferation. Moreover, ERBB3 seems to contribute to T1DM pathogenesis by modulating antigen-presenting cell function and autoimmunity as well as beta-cell apoptosis and insulin production. Therefore, the aim of this study was to investigate the association of the rs2292239 (C/A) polymorphism in the ERBB3 gene with susceptibility to T1DM in a Brazilian population from Southern-Brazil.

Methods: Frequencies of the rs2292239 polymorphism were analyzed in 461 T1DM patients (cases) and 570 non-diabetic subjects (controls). Genotyping was performed using Real-Time PCR and TaqMan MGB probes (Thermo Scientific).

Results: Genotype distributions of the ERBB3 rs2292239 polymorphism were in agreement with those predicted by the Hardy-Weinberg Equilibrium in the control group (P ≥0.05), with the A/A genotype being more frequent in T1DM patients compared with non-diabetic subjects (P=0.007). The A allele frequency was 39.7% in the T1DM group and 32.8% in the control group (P=0.008). Moreover, the A allele was significantly associated with T1DM risk when taking into account additive (OR=1.67, 95% CI 1.07 – 2.61; P=0.023) and recessive (OR=1.58, 95% CI 1.04 – 2.40; P=0.031) inheritance models, adjusting for T1DM high-risk HLA- DR/DQ haplotypes. In conclusion, our data confirms the association between the ERBB3 rs2292239 and risk for T1DM in a population from Southern-Brazil.