Avaliação do polimorfismo de deleção de GSTT1 e GSTM1 na susceptibilidade ao diabetes mellitus tipo 2

• Autor(a) principal: Pinheiro, Denise da Silva
• Data de Publicação: 2013
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• dARK ID: ark:/38995/001300000275b
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/3482
• topic: Diabetes mellitus; Susceptibilidade genética; Polimorfismo; GSTM1; GSTT1; Genetic susceptibility; Polymorphism; BIOQUIMICA::BIOLOGIA MOLECULAR

In the pathogenesis of type 2 diabetes mellitus (DM2), it is observed that the increased oxidative stress may contribute to decreased insulin production and destruction of pancreatic β cells. Individuals who have no activity of GSTM1 and GSTT1 isoforms may have an increased susceptibility to damage caused by reactive species to pancreatic β cells, since these cells express low levels of antioxidant enzymes. This case-control study aimed to analyze the genotypic profiles of the deletion polymorphism of GSTM1 and GSTT1 genes by molecular assays (conventional PCR and qPCR) to associate these polymorphisms with DM2 risk, considering that studies with this approach have not been conducted in Brazil. Data of clinical, laboratorial and demographic variables of 120 patients and 147 controls were obtained through interviews and information from medical charts (patients) or results of recent clinical and laboratory exams (controls). It was found that diabetic patients had a higher frequency of GSTT1-null genotype (29.2%) than non-diabetic subjects (12.2%), and those with the risk genotype have an increased predisposition to diabetes from approximately 3.2 times (p = 0.0004). However, there was no association of GSTM1-null with DM2 susceptibility. The analysis of the influence of GSTT1 deletion on clinical and biochemical changes in the case group showed that the risk genotype may contribute to the development of DM2 complications related to dyslipidemia, due to the association of GSTT1-null with significantly higher levels of triglycerides (p = 0.0242) and VLDL-cholesterol levels (p = 0.0252) compared to patients without the risk genotype. Additionally, GSTM1-null was associated with elevated levels of fasting glucose, glycated hemoglobin and blood pressure. We emphasized a necessity for applying log-linear analysis in order to explore an interaction between these polymorphisms properly. These results suggest that GSTT1 polymorphism may play an important role in the pathogenesis of DM2 in Brazilian population. Then, this gene could be added to a set of genetic markers to identify individuals at increased risk for developing DM2. Although there was no association of GSTM1 deletion polymorphism with susceptibility to DM2, it was verified the influence of this polymorphism on important clinical parameters related to glycemia and blood pressure levels. This finding suggests that GSTM1-null, GSTT1-null as well, may contribute to the clinical course of diabetic patients.