Avaliação molecular dos polimorfismos genéticos na susceptibilidade à nefropatia diabética por alterações hemodinâmicas e endoteliais

Abstract

Diabetic nephropathy (DN) is the major microvascular complication of Diabetes mellitus (DM) and is among the leading causes of kidney disease. This pathology is important because of glomerular changes induced by imbalance of glucose homeostasis and high intraglomerular pressure. Studies indicate that diseases are influenced not only by the environment but also by genetic factors. Among the genetic determinants, the polymorphisms in the MTHFR and VEGF genes stand out. These genes are oriented towards the synthesis of the enzyme methylenetetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF), respectively. The MTHFR enzyme plays an important role in the processing and processing cycle of methionine. VEGF is an important protein involved in signaling that stimulates vasculogenesis and angiogenesis. Thus, the objective of this study was to perform a molecular evaluation of MTHFR C677T and VEGF -141 A → C single nucleotide polymorphisms (SNPs) in diabetic patients with microvascular complications caused by hemodynamic and endothelial changes in a Brazilian population. A total of 345 were genotyped for polymorphisms using PCR-RFLP. The advanced RStúdio environment was used for statistical analysis. The logistic regression of the gene polymorphism in the MTHFR gene increases the risk (OR = 2.57, p = 0.003) of the diabetic individual developing ND. The polymorphism in VEGF gene reveals a 3.74-fold risk for DN (p = 0.001) in the eventual condition of diabetic patient. When analyzing the association of clinical variables and polymorphism in the MTHFR gene, the results showed no correlation. The association of clinical variables with the VEGF gene polymorphism, the results indicated the same in creatinine, in GFR and in diastolic blood pressure. Clinical associations observe a mechanism underlying the role of polymorphisms in renal dysfunction. Results suggest that polymorphisms MTHFR gene confer susceptibility to ND in the patients with DM.