Gene networks comparison to understand the effects of glucose toxic and genetic variants in the Type 2 Diabetes Mellitus risk.

• Grant number: 12/14097-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2013
• End date: December 08, 2015
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Alexandre da Costa Pereira
• Grantee: André Ramos Vaquero
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Type 2 Diabetes Mellitus (T2DM) results from the interaction between genetic and environmental risk factors, being characterized by high blood glucose levels, insulin resistance and, at a late stage, reduced insulin secretion by pancreatic ²-cells. Recently, the genetic study has been one of the most used approaches to the understanding of this disease, trying to identify the genes that are responsible for the multifactorial disease characteristics and the interactions of these genes with environmental factors. The present study provides continuity to the study "Comparative study of gene expression networks with genes associated with type 2 diabetes mellitus (T2DM) and risk genotypes for disease", and its purpose is to investigate possible genetic and environmental factors that influence the T2DM pathology in 100 vascular smooth muscle cell samples. In order to analyze the contribution of the most significant genetic markers associated with T2DM risk and of the blood glucose toxic levels to the disease risk we will use expression levels and expression correlation comparison approaches. The applied technique to measure gene expression levels will be the RNA-seq, so that we are going to quantify all mRNA in the cells in order to analyze expression: of the genes that harbor or are close to T2DM associated polymorphisms, as well as the genes that participate in their signaling pathways, and genes that participate in T2DM signaling pathways. The pattern comparisons will be made for each polymorphism between patients with and without the considered T2DM risk allele, and between subjects before and after glucose treatment in cell culture; and such comparisons will be simply represented as a network of gene interactions. Based on current knowledge, we believe that the resulting connectivity diagram between genes related to T2DM allows us to examine the behavior of the entire group of genes and how genes can interact, giving us an advance of the disease pathology understanding.