Associação de polimorfismos em genes de citocinas com complicações microvasculares e comorbidades no Diabetes mellitus tipo 2

Abstract

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia and it shows a high morbidity and mortality with losses in the patients quality of life. In recent decades, several studies have showed that the pathogenesis of T2D and its complications are associated with a chronic inflammatory state and the low-grade activation of the innate immune system. The production of pro- and anti-inflammatory cytokines as well as acute phase markers can trigger a series of signaling pathways which culminate in insulin resistance and the development of the disease. The aim of this study was to evaluate the association of polymorphisms in cytokines genes (TNF-á - 308G/A, IL-10 -1082G/A, IL-10 -819T/C, IL-10 -592C/A, TGF-â1 codon 10 T/C, TGF-â1 codon 25 C/G, IL-6 -174G/C, and IFN-ã +874T/A) with retinopathy, nephropathy, and neuropathy; as well as to hypertension, dyslipidemia, and obesity in individuals with T2D. We selected 102 patients with clinical and laboratorial diagnosis of T2D. The genotyping were performed by allele-specific PCR. The classification of complications and comorbidities were applied according to the American Diabetes Association. Retinopathy was associated with GG genotype and G allele in TGF-â1 codon 25 C/G polymorphism and the nephropathy was associated with the lower frequency of GG genotype in IL-10 - 1082G/A polymorphism. Hypertension was associated with the CC genotype and C allele for IL-10 -592C/A polymorphism, and higher frequencies of T and C alleles of the TGF-â1 codon 10 T/C and IL-10 -819T/C polymorphisms, respectively. The TGF-â1 codon 10 T/C polymorphism was associated with the BMI groups: the CC genotype was more frequent in the group with BMI < 25 Kg/m2, while the TC genotype was more frequent in the group with BMI 30 Kg/m2. The results suggest that polymorphisms in cytokine genes are related to complications and comorbidities in T2D, indicating that inflammation contributes to the pathogenesis of these clinical changes.