在心血管队列中，人类 RAD52 基因的常见单核苷酸多态性与年龄调整后死亡风险增加相关。

Increased age-adjusted hazard of death associated with a common single nucleotide polymorphism of the human RAD52 gene in a cardiovascular cohort.

机构信息

Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Building A18, 625 00, Brno, Czech Republic; Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice 5, Building A29, 625 00, Brno, Czech Republic.

出版信息

Mech Ageing Dev. 2017 Oct;167:56-63. doi: 10.1016/j.mad.2017.10.003. Epub 2017 Oct 9.

DOI:10.1016/j.mad.2017.10.003

PMID:29024686

Abstract

Aging may be characterized as the progressive increase of the risk of death caused by a decrease of almost all bodily functions. While a great number of model organism studies have established the role of DNA double strand breaks (DSBs) as one of the main causes of aging, few studies have examined whether common polymorphisms in human DSB repair genes influence aging and mortality. More importantly, to the best of our knowledge, no longitudinal study has thus far examined the link between polymorphisms in DSB repair and the risk of death. This longitudinal study thus analyses whether four common polymorphisms (rs2155209, rs7963551, rs17105278, rs2735383) in four selected DSB repair genes (MRE11A, RAD52, RAD51B, NBS1) influence the hazard of age-adjusted death in a cohort of patients with typical symptoms of ischemic heart disease. The results have shown that rs7963551 G/T heterozygotes exhibit a significantly increased hazard of death when compared with the combined GG and TT homozygotes (HR=1.42, 95% CI: 1.06-1.91, p=0.018). This study indicates that the SNP affecting efficiency of DSB repair may influence aging in humans.

摘要

衰老是指由于几乎所有身体机能的下降，导致死亡风险逐渐增加的过程。虽然大量的模式生物研究已经确定了 DNA 双链断裂（DSB）作为衰老的主要原因之一，但很少有研究检查人类 DSB 修复基因中的常见多态性是否会影响衰老和死亡率。更重要的是，据我们所知，迄今为止还没有纵向研究检查 DSB 修复中的多态性与死亡风险之间的联系。因此，这项纵向研究分析了四个选定的 DSB 修复基因（MRE11A、RAD52、RAD51B 和 NBS1）中的四个常见多态性（rs2155209、rs7963551、rs17105278 和 rs2735383）是否会影响一组有典型缺血性心脏病症状的患者的年龄调整后死亡风险。结果表明，与 GG 和 TT 纯合子相比，rs7963551 G/T 杂合子的死亡风险显著增加（HR=1.42，95%CI：1.06-1.91，p=0.018）。这项研究表明，影响 DSB 修复效率的 SNP 可能会影响人类的衰老。