Análise in silico de polimorfismos de um único nucleotídeo (SNPs) em diabetes tipo 2 em humanos

Abstract

Increase in actions aiming at expanding life expectancy also increase the risk of manifestation of age-related disorders. Type 2 diabetes appears as one of the main chronic diseases associated with aging, characterized by persistent hyperglycemia. This occurs due to impaired insulin secretion by beta-pancreatic cells, resulting in negative impact on life quality of the affected individual, caused by manifestation of several pathologies associated with high blood glucose levels. Elucidation of complex mechanisms which generates disorders of blood glucose homeostasis involves knowledge of genetic influence associated with diabetes manifestation. In this context, the present study aimed to identify genetic variants in coding regions of four genes (FKH1, PDX1, TP53 and TCF7L2) and to estimate genetic diversity parameters inside groups of healthy or type 2 diabetes previously diagnosed individuals, based on the analysis of consensus sequences obtained from next-generation sequencing fragments (reads) available at NCBI database. Reads were mapped to DNA coding sequences (CDS) corresponding to candidate genes using Geneious software. Consensus sequences obtained were aligned using MEGA X software, and main intra and interpopulation diversity descriptors were estimated using DnaSP software. Low nucleotide diversity was observed among populations sampled, although polymorphic sites and different haplotypes were identified. Single nucleotide polymorphisms (SNPs) were identified and correlated with risk of disease manifestation within each population, using SNPStats platform. Results suggest being possible to trace exome variants that can be associated with the risk of type 2 diabetes development in human populations, mainly for FOXO1 and TCF7L2.