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, both civilians and Veterans are or have been overweight or obese. Surprisingly, the majority of the obese subjects, Veterans or non-veterans, 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 DNA was isolated. Samples were subjected to next-generation exome sequencing that was followed by comprehensive bioinformatics analysis. Several promising SNVs in the three genes, with p<0.05, associated specifically with T2D in the obese individuals have been already identified. Determination of their position revealed that all of the T2D-asssociated SNPs are located in the noncoding regions of the three genes. Among those, of particular interest are T2D-associated super enhancer SNVs identified in the PIKFYVE gene of fat tissue. We are currently extending our observations by comparing our findings with those available in database or by other research groups to gain novel insights in the pathogeneses of T2D in obesity.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Nov 01, 2018
Accession Number
AD1095374

Entities

People

  • Assia Shisheva
  • Berhane Seyoum
  • Diego Sbrissa
  • Ognian Ikonomov

Organizations

  • Wayne State University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • African Americans
  • Biomedical Information Systems
  • Biomedical Research
  • Computational Biology
  • Demographic Cohorts
  • Department Of Defense
  • Diabetes
  • Diabetes Mellitus
  • Fat Cells
  • Genetics
  • Glucose Metabolism Disorders
  • Nucleotides
  • Obesity
  • Overweight
  • Quality Control
  • Sequences
  • Type 2 Diabetes

Fields of Study

  • Biology

Readers

  • Astronomy and Astrophysics.
  • Molecular and Cellular Biology
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology