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Physical health and incident late-life depression: modification by cytokine genes.身体健康与晚年抑郁症发病：细胞因子基因的修饰作用。
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UCP3 polymorphisms, hand grip performance and survival at old age: association analysis in two Danish middle aged and elderly cohorts.UCP3 多态性、握力表现与老年生存：两项丹麦中老年队列的关联分析。
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Associations between inflammatory markers, candidate polymorphisms and physical performance in older Danish twins.丹麦老年双胞胎中炎症标志物、候选多态性与身体机能表现的相关性研究。
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本文引用的文献

1
Rejuvenation of the aging T cell compartment.衰老T细胞库的年轻化。
Curr Opin Immunol. 2009 Aug;21(4):454-9. doi: 10.1016/j.coi.2009.06.002. Epub 2009 Jul 14.
2
Arlequin (version 3.0): an integrated software package for population genetics data analysis.Arlequin（版本 3.0）：一个用于群体遗传学数据分析的集成软件包。
Evol Bioinform Online. 2007 Feb 23;1:47-50.
3
Interleukin-18 promoter polymorphisms and risk of late onset Alzheimer's disease.白细胞介素-18启动子多态性与晚发型阿尔茨海默病风险
Brain Res. 2009 Feb 9;1253:169-75. doi: 10.1016/j.brainres.2008.11.083. Epub 2008 Dec 3.
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Sex-specific genetic architecture of human disease.人类疾病的性别特异性遗传结构。
Nat Rev Genet. 2008 Dec;9(12):911-22. doi: 10.1038/nrg2415.
5
Effect of interleukin-6 polymorphisms on human longevity: a systematic review and meta-analysis.白细胞介素-6基因多态性对人类寿命的影响：一项系统评价和荟萃分析。
Ageing Res Rev. 2009 Jan;8(1):36-42. doi: 10.1016/j.arr.2008.09.001. Epub 2008 Sep 27.
6
Lack of association between TNF-alpha polymorphisms and Alzheimer's disease in an Italian cohort.意大利队列中肿瘤坏死因子-α基因多态性与阿尔茨海默病之间无关联。
Neurosci Lett. 2008 Dec 3;446(2-3):139-42. doi: 10.1016/j.neulet.2008.09.044.
7
Joint analysis of individual participants' data from 17 studies on the association of the IL6 variant -174G>C with circulating glucose levels, interleukin-6 levels, and body mass index.对17项关于IL6基因变体-174G>C与循环葡萄糖水平、白细胞介素-6水平及体重指数之间关联的研究中个体参与者的数据进行联合分析。
Ann Med. 2009;41(2):128-38. doi: 10.1080/07853890802337037.
8
Exceptional longevity does not result in excessive levels of disability.超长寿命并不会导致过度残疾。
Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13274-9. doi: 10.1073/pnas.0804931105. Epub 2008 Aug 18.
9
TNF promoter polymorphisms associated with muscle phenotypes in humans.与人类肌肉表型相关的肿瘤坏死因子启动子多态性
J Appl Physiol (1985). 2008 Sep;105(3):859-67. doi: 10.1152/japplphysiol.90655.2008. Epub 2008 Jul 17.
10
A genetic-demographic approach reveals male-specific association between survival and tumor necrosis factor (A/G)-308 polymorphism.一种遗传人口学方法揭示了生存与肿瘤坏死因子（A/G）-308多态性之间的男性特异性关联。
J Gerontol A Biol Sci Med Sci. 2008 May;63(5):454-60. doi: 10.1093/gerona/63.5.454.

在 90 岁以上的人群中，常见的炎症细胞因子基因多态性研究仅显示出对死亡率和相关危险因素的微小影响。

Commonly studied polymorphisms in inflammatory cytokine genes show only minor effects on mortality and related risk factors in nonagenarians.

机构信息

The Danish Aging Research Center, Epidemiology Unit, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 9, DK-5000 Odense, Denmark.

出版信息

J Gerontol A Biol Sci Med Sci. 2010 Mar;65(3):225-35. doi: 10.1093/gerona/glp210. Epub 2010 Jan 18.

DOI:10.1093/gerona/glp210
PMID:20083555
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2822285/
Abstract

Systemic low-grade inflammation is consistently associated with functional status, cognitive functioning, multimorbidity, and survival in oldest olds. If inflammation is either a cause or a consequence of age-related pathology, genetic determinants of late-life survival can reside in cytokine genes polymorphisms, regulating inflammatory responses. The aim of this study was to test associations between commonly studied polymorphisms in interleukin (IL)6, IL10, IL15, and IL18, and tumor necrosis factor-alpha genes and late-life survival in a longitudinal cohort of nonagenarians: the Danish 1905 cohort. Additionally, associations were investigated between inflammatory markers and major predictors of mortality as cognitive and functional status. Modest sex-specific associations were found with survival, cognitive functioning, and handgrip strength. Evaluation of combined genotypes indicated that, in nonagenarian men, the balance of pro- and anti-inflammatory activity at IL18 and IL10 loci is protective against cognitive decline. In conclusion, in this large study with virtually complete follow-up, commonly studied polymorphisms in cytokine genes do not have a major impact on late-life survival or associated risk phenotypes.

摘要

全身性低度炎症与功能状态、认知功能、多种疾病和最年长老年人的生存一直相关。如果炎症是与年龄相关的病理的原因或结果，那么调节炎症反应的细胞因子基因多态性可能是与晚年生存相关的遗传决定因素。本研究的目的是在丹麦 1905 队列的一个纵向队列中，检验白细胞介素 (IL)6、IL10、IL15 和 IL18 以及肿瘤坏死因子-α 基因中常见的多态性与寿命的关联。此外，还研究了炎症标志物与认知和功能状态等死亡率主要预测因素之间的关联。结果发现，与生存、认知功能和握力有适度的性别特异性关联。对组合基因型的评估表明，在 90 岁以上的男性中，IL18 和 IL10 位点促炎和抗炎活性的平衡对认知能力下降具有保护作用。总之，在这项几乎完全随访的大型研究中，细胞因子基因的常见多态性对晚年生存或相关风险表型没有重大影响。