Functional Genetics for Predisposition to Development of Type 2 Diabetes in Obese Individuals
Abstract
T2D frequently occurs together with obesity. In fact, the vast majorities of T2D individuals from both civilian and Veteran populations are or have been overweight or obese. Surprisingly, the majority of the obese subjects, both Veterans and non-veterans, will never develop T2D and their metabolic tissues will never lose the ability to respond to insulin. This fact indicates the critical role of the genetic predisposition to T2D development in obesity. The proposal assesses for the first time if pathogenic single nucleotide variations (SNVs) within three genes, i.e., PIKFYVE, FIG4 and/or VAC14, found previously to be involved in glucose homeostasis, are linked with T2D development in obese individuals. The expected changes will be related to functional differences in the performance of the PIKfyve enzymatic activity. A total of 96 obese patients with or without T2D (DM and non-DM), 48 per group, with similar average BMI and age have been selected and included in the analyses. Fat tissue for analyses has been collected and the DNA was isolated. Samples were subjected to next-generation exome sequencing. Several promising SNVs in the three genes, with p < 0.05, associated specifically with T2D in the obese individuals have been already identified. Determining their position within the gene and the potential functional outcome is currently in progress.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2018
- Accession Number
- AD1053927
Entities
People
- Assia Shisheva
- Berhane Seyoum
- Diego Sbrissa
- Ognian Ikonomov
Organizations
- Wayne State University