Dato Serena, De Rango Francesco, Crocco Paolina, Passarino Giuseppe, Rose Giuseppina
Department of Biology, Ecology and Earth Science, University of Calabria, Ponte Pietro Bucci Cubo 4C, 87036, Rende, CS, Italy.
Biogerontology. 2017 Jun;18(3):347-355. doi: 10.1007/s10522-017-9690-z. Epub 2017 Mar 9.
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 (p = 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.
端粒缩短率已被广泛报道为人类人群中与年龄相关疾病和死亡率风险的标志物。遗传、环境和随机因素已被证明会影响端粒损耗。特别是氧化应激已被报道在这一过程中起重要作用。解偶联蛋白（UCPs）是细胞代谢和氧化应激最重要的调节因子之一。几位作者研究了健康和不健康（受糖尿病影响）受试者中UCP基因变异与白细胞端粒长度（LTL）的关联，报告了相互矛盾的结果。我们通过分析457名年龄在64 - 105岁之间的受试者队列中的这些多态性，测试了UCP2 - UCP3基因组区域中四个单核苷酸多态性（SNPs）对LTL和葡萄糖代谢的影响。在85岁以下的受试者中，两个UCP2变体（rs659366 - A和rs660339 - T）的次要等位基因纯合子的LTL比其他基因型短（p = 0.024）。在相同样本中，发现AA - rs659366基因型与糖化血红蛋白的血液学水平较低相关（分别为p = 0.012和p = 0.022）。此外，在一小部分患者中，UCP2的rs659366 - AA和UCP3的rs15673 - TT与糖尿病相关。此处呈现的结果表明，UCP变异性具有不同的多效性作用，可能通过影响能量代谢和应激反应，对端粒长度和葡萄糖稳态均产生影响。
