title: Pleiotropic effects of UCP2-UCP3 variability on leucocyte telomere length and glucose homeostasis.
abstract: The rate of telomere-shortening has been widely reported as a marker of risk for age-related conditions and mortality in human population. Genetic, environmental and stochastic factors have been shown to influence telomere attrition. In particular oxidative stress has been reported to play an important role on the process. Uncoupling proteins (UCPs) are among the most important regulators of cellular metabolism and oxidative stress. Several authors investigated the association of UCP genetic variants with leucocyte telomere length (LTL) in both healthy and unhealthy (affected by diabetes) subjects, reporting contrasting results. We tested the influence of four SNPs falling in UCP2-UCP3 genomic region on LTL and glucose metabolism by analyzing these polymorphisms in a cohort of 457 subjects, in an age range 64-105 years. Among subjects younger than 85 years, homozygotes for the minor alleles at two UCP2 variants (rs659366-A and rs660339-T) showed shorter LTL respect to the other genotypes (pmodel= 0.024). In the same samples, AA-rs659366 genotype was found associated with lower haematological levels of Glycosylate Haemoglobyn (p = 0.012 and p = 0.022, respectively). Furthermore, rs659366-AA at UCP2 and rs15673-TT at UCP3 were correlated to diabetes in a small sub-group of patients. Results here presented suggest that UCP variability has different pleiotropic effects, by affecting both telomere length and glucose homeostasis, likely through an influence on energy metabolism and stress response.
authors.affiliation: Department of Biology, Ecology and Earth Science, University of Calabria, Ponte Pietro Bucci Cubo 4C, 87036, Rende, CS, Italy. serena.dato@unical.it.
authors.forename: Serena
authors.identifier: 0000-0003-2589-7929
authors.initials: S
authors.lastname: Dato
authors.affiliation: Department of Biology, Ecology and Earth Science, University of Calabria, Ponte Pietro Bucci Cubo 4C, 87036, Rende, CS, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: De Rango
authors.affiliation: Department of Biology, Ecology and Earth Science, University of Calabria, Ponte Pietro Bucci Cubo 4C, 87036, Rende, CS, Italy.
authors.forename: Paolina
authors.initials: P
authors.lastname: Crocco
authors.affiliation: Department of Biology, Ecology and Earth Science, University of Calabria, Ponte Pietro Bucci Cubo 4C, 87036, Rende, CS, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passarino
authors.affiliation: Department of Biology, Ecology and Earth Science, University of Calabria, Ponte Pietro Bucci Cubo 4C, 87036, Rende, CS, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rose
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D016615:Telomere; D000071246:Uncoupling Protein 2 / Q000235:genetics*; D000071247:Uncoupling Protein 3 / Q000235:genetics*
chemical_list: C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D005947:Glucose
keywords: Aging; Glucose homeostasis; Glycosilated haemoglobin; Leucocyte telomere length (LTL); Mitochondrial uncoupling protein