Estudo da associação dos genes TLR2, TLR4, MYD88, NFKB, MCP1/CCL2 e IL18 com o desenvolvimento da nefropatia em pacientes com diabetes mellitus tipo 1

Abstract

Inflammation has been described as an important development factor for chronic diseases, such as diabetes and the condition of hyperglycemia would be responsible for activation of toll-like receptors (TLRs) and cytokines and consequently the induction of local and systemic inflammation. In this sense, the objective of this study was to evaluate the association of the mRNA expression of TLR2, TLR4, MYD88, NFKB, MCP1/CCL2 and IL18 genes in peripheral blood mononuclear cells of children, adolescents and young adults with type 1 diabetes with pro-inflammatory state of Diabetes mellitus type 1 (DM1) and abnormal renal function. 49 normoglycemic individuals (NG) and 49 patients with DM1, between 6 and 20 years were studied. Diabetic patients were analyzed as a whole (group DM1), and subdivided into two groups according to glycemic control: offset diabetics (DM1C group) and diabetic uncompensated (DM1NC group). We evaluated fasting glucose, glycated hemoglobin, urea, serum creatinine, total protein fractions and albumin/creatinine ratio (ACR) urinary individuals studied. mRNA expression of TLR2, TLR4, MYD88, NFKB, MCP1/CCL2 and IL18 genes was also determined using the technique of real time PCR (Taqman ®). Most individuals with DM1 (65.3%) had poor glycemic control (glycated hemoglobin >8%). With respect to renal function, we observed a significant increase in the values of ACR groups DM1(p=0.006) and DM1NC(p=0.008) compared to NG. Regarding the biochemical markers such as total protein fractions (p=0.044) and an increase in serum concentrations of total protein in DM1 group, and concentrations of globulins in DM1(p<0.001), DM1C(p<0.001) and DM1NC (p<0.001) group when compared to the NG group. In the molecular analysis, significant increase in the expression of TLR2 (p = 0.003), TLR4 (p = 0.006), MYD88 (p = 0.015) and NFKB (p = 0.035) for DM1 group compared to NG were observed. A significantly increased expression of TLR2 (p=0.017) e NFKB (p=0.035) to DM1NC group compared to NG was also observed. No significant differences were observed in expression of IL18 and MCP1/CCL2 between groups and subgroups. These results suggest that poor glycemic control, together with the presence of risk factors and the inflammatory state associated with hyperglycemia may be mediated by activation of TLR-2 and TLR-4, which may contribute to the development of future complications, such as diabetic nephropathy.