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Functional genetics for predisposition to development of Type 2 Diabetes in obese individuals

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Technical Report,01 Jan 2018,14 Oct 2018

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Wayne State University Detroit United States

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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 andor 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 p0.05, 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.

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  • Medicine and Medical Research

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