Shortened Leukocyte Telomere Length in Type 2 Diabetes Mellitus: Genetic Polymorphisms in Mitochondrial Uncoupling Proteins and Telomeric Pathways

Overview

Journal Clin Transl Med

Publisher Wiley

Specialty General Medicine

Date 2016 Mar 9

PMID 26951191

Citations 16

Authors

Yuling Zhou

Zhixin Ning

Yvonne Lee

Brett D Hambly

Craig S McLachlan

Affiliations

Soon will be listed here.

Abstract

Current debate in type 2 diabetes (T2DM) has focused on shortened leukocyte telomere length (LTL) as the result of a number of possible causes, including polymorphisms in mitochondrial uncoupling proteins (UCPs) leading to oxidative stress, telomere regulatory pathway gene polymorphisms, or as a direct result of associated cardiovascular complications inducing tissue organ inflammation and oxidative stress. There is evidence that a heritable shorter telomere trait is a risk factor for development of T2DM. This review discusses the contribution and balance of genetic regulation of UCPs and telomere pathways in the context of T2DM. We discuss genotypes that are well known to influence the shortening of LTL, in particular OBFC1 and telomerase genotypes such as TERC. Interestingly, the interaction between short telomeres and T2DM risk appears to involve mitochondrial dysfunction as an intermediate process. A hypothesis is presented that genetic heterogeneity within UCPs may directly affect oxidative stress that feeds back to influence the fine balance of telomere regulation, cell cycle regulation and diabetes risk and/or metabolic disease progression.

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