Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Centre for Ageing and Health (AgeCap) at the University of Gothenburg, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
J Gerontol A Biol Sci Med Sci. 2018 Oct 8;73(11):1453-1458. doi: 10.1093/gerona/gly021.
Self-rated health (SRH) strongly predicts mortality. Twin studies estimate that genetic factors account for a substantial part of the variability in SRH. Variations in the gene FOXO3 (forkhead box O3), and in genes located at the APOE (apoplipoprotein E) locus, are associated with longevity. This study explores the relationship between SRH and genetic variation related to longevity, in a population-based cohort of older individuals. SRH was assessed among 1,520 individuals aged 75-87, and five single nucleotide polymorphisms (SNPs), in APOE, TOMM40 (translocase of outer mitochondrial membrane 40 homolog), and FOXO3 were genotyped. Two SNPs (rs10457180 and rs2802292) in FOXO3 were associated with SRH (OR = 2.18 [CI: 1.27-3.76], p = .005 and OR = 1.63 [CI: 1.11-2.40], p = .013), while no associations were found with SNPs in APOE and TOMM40. Several factors, such as depression, cardiovascular disease (CVD), and diabetes, were related to SRH, but the only factor that had any influence on the association with FOXO3 was CVD. Still, after including CVD as a covariate, the associations between FOXO3 SNPs and SRH remained significant. Our results suggest that FOXO3 is related to SRH in older individuals. This relationship seems to be influenced by CVD, but not by mental and cognitive status.
自评健康（SRH）强烈预测死亡率。双胞胎研究估计，遗传因素在 SRH 的可变性中占很大一部分。FOXO3（叉头框 O3）基因和位于 APOE（载脂蛋白 E）基因座的基因的变异与长寿有关。本研究在一个基于人群的老年个体队列中探讨了 SRH 与与长寿相关的遗传变异之间的关系。在 1520 名年龄在 75-87 岁的个体中评估了 SRH，并对 APOE、TOMM40（外线粒体膜转运蛋白 40 同源物）和 FOXO3 中的五个单核苷酸多态性（SNP）进行了基因分型。FOXO3 中的两个 SNP（rs10457180 和 rs2802292）与 SRH 相关（OR=2.18[CI：1.27-3.76]，p=0.005 和 OR=1.63[CI：1.11-2.40]，p=0.013），而 APOE 和 TOMM40 中的 SNP 与 SRH 无关。一些因素，如抑郁、心血管疾病（CVD）和糖尿病，与 SRH 有关，但与 FOXO3 相关的唯一因素是 CVD。尽管如此，在将 CVD 作为协变量纳入后，FOXO3 SNP 与 SRH 之间的关联仍然显著。我们的结果表明，FOXO3 与老年个体的 SRH 有关。这种关系似乎受 CVD 影响，但不受精神和认知状态影响。
