title: Shortened leukocyte telomere length in type 2 diabetes mellitus: genetic polymorphisms in mitochondrial uncoupling proteins and telomeric pathways.
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.
authors.affiliation: Faculty of Medicine, Rural Clinical School, University of New South Wales, Samuels Building, Level 3, Room 327, Sydney, 2052, Australia. zhouyuling20120901@gmail.com.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Faculty of Medicine, Rural Clinical School, University of New South Wales, Samuels Building, Level 3, Room 327, Sydney, 2052, Australia. z.ning@student.unsw.edu.au.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Faculty of Medicine, Rural Clinical School, University of New South Wales, Samuels Building, Level 3, Room 327, Sydney, 2052, Australia. yvonne.lee3@yahoo.com.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Discipline of Pathology, Bosch Institute, Sydney Medical School, University of Sydney, Sydney, Australia. brett.hambly@sydney.edu.au.
authors.forename: Brett D
authors.initials: BD
authors.lastname: Hambly
authors.affiliation: Faculty of Medicine, Rural Clinical School, University of New South Wales, Samuels Building, Level 3, Room 327, Sydney, 2052, Australia. reperfusion@hotmail.com.
authors.forename: Craig S
authors.initials: CS
authors.lastname: McLachlan
keywords: Genetics; Telomere length; Telomere-associated pathway genes; Type 2 diabetes; Uncoupling protein polymorphisms