PNAS2014-04-29 4:40 PM

社会贫困,遗传敏感性和儿童端粒长度 Social disadvantage, genetic sensitivity, and children's telomere length. 

论文摘要
处境不利的社会环境与不良健康结果相关联。这在某种程度上归因于慢性应激。端粒长度(TL)已被用作慢性应激的生物标志物:身处包括不利社会地位和抑郁症在内的各种情况中的成年人的 TL较短。我们使用40名参与脆弱家庭和儿童福利研究的9岁男孩的数据来将这一观测延伸至非洲裔儿童。我们的报告表明弱势环境的生活与9岁男孩TL长度的减少相关。我们的研究记录表明低收入,母亲受教育低,不稳定家庭结构以及严厉家教和TL长度之间具有显著关联。这些影响受血清素和多巴胺能通路中的遗传变量的控制影响。与微分磁化率易感性的假说一致,遗传敏感性得分最高的受测者主体在 暴露在不利社会环境中时具有最短TL,而让其身处有利社会环境时则具有最长TL。

Abstract
Disadvantaged social environments are associated with adverse health outcomes. This has been attributed, in part, to chronic stress. Telomere length (TL) has been used as a biomarker of chronic stress: TL is shorter in adults in a variety of contexts, including disadvantaged social standing and depression. We use data from 40, 9-y-old boys participating in the Fragile Families and Child Wellbeing Study to extend this observation to African American children. We report that exposure to disadvantaged environments is associated with reduced TL by age 9 y. We document significant associations between low income, low maternal education, unstable family structure, and harsh parenting and TL. These effects were moderated by genetic variants in serotonergic and dopaminergic pathways. Consistent with the differential susceptibility hypothesis, subjects with the highest genetic sensitivity scores had the shortest TL when exposed to disadvantaged social environments and the longest TL when exposed to advantaged environments.


意义
本文对社会环境和健康间的研究作出了两项贡献。 从出生队列研究所得的数据我们发现,在非裔美国男孩中,那些在高度弱势的家庭环境中长大的男孩有较短端粒(9岁),而那些在高度有利环境中长大的男孩则端粒较长。我们还发现,社会环境和端粒长度(TL)之间的关联受羟色胺和多巴胺途径内的遗传变异控制影响。当遗传灵敏度最高得分的男孩生活在最差社会环境中时则显示出最短TL,而让他接触最优社会环境则表现出最长TL。据我们所知,该报告是记录TL作为应激暴露的生物标志物受基因和社会环境相互作用的首份记录。

Significance
This paper makes two contributions to research on the link between the social environment and health. Using data from a birth cohort study, we show that, among African American boys, those who grow up in highly disadvantaged environments have shorter telomeres (at age 9) than boys who grow up in highly advantaged environments. We also find that the association between the social environment and telomere length (TL) is moderated by genetic variation within the serotonin and dopamine pathways. Boys with the highest genetic sensitivity scores had the shortest TL when exposed to disadvantaged environments and the longest TL when exposed to advantaged environments. To our knowledge, this report is the first to document a gene–social environment interaction for TL, a biomarker of stress exposure.

————————————————

唧唧堂调查

科学家们对 9 岁的儿童进行研究发现,贫穷和不稳定的家庭环境会缩短他们染色体上的保护结构——端粒。这种老化现象也从某种程度上解释了生活在贫穷或强大压力下的成年人容易患上严重疾病的原因。
一项针对非裔美国男孩的研究显示,在紧张而充满压力的社会环境中成长,会给儿童染色体留下持久的印迹。端粒是保护染色体末端免遭磨损的重复性 DNA 序列,而研究人员发现,与家庭条件较好的儿童相比,贫困和不稳定家庭中的儿童端粒更短。
端粒的长度往往被认为是慢性压力的生物学标志。研究人员对来自美国主要城市的 40 名 9 岁男孩进行了 DNA 检测,发现家庭环境较差的儿童的端粒,比家庭背景较好的儿童短 19%。相关研究论文刊登在了近期出版的《PNAS》杂志上。
加州大学健康心理学家 Elissa Epel(未参与本研究)评论道,这项研究让人们得以进一步理解,童年时期的社会条件会对长期健康产生怎样的影响。
这项研究中的 DNA 样本和社会经济学数据,来自于一项由美国NIH资助的大型项目。这个被称为 Fragile Families and Child Wellbeing Study 的研究跟踪调查了近五千名儿童,这些儿童大多于 1998 年-2000 年间出生在美国大城市的单亲家庭。据领导这项研究的宾州大学分子生物学家 Daniel Notterman 介绍,文中对儿童环境的评估是基于母亲的教育程度、家庭收入和支出情况、教育的严厉程度、以及家庭结构的稳定性。
研究指出,与母亲未完成高中学业的男孩相比,母亲获得高中以上学历的男孩端粒要长 32%。另外,与家庭结构多变的儿童相比,稳定家庭的儿童端粒要长 40%。
遗传学关联
5-羟色胺和多巴胺是大脑中两个重要的神经递质,研究人员发现,这两种递质相关通路中的遗传学突变,介导了家庭环境与端粒长度之间的关联。举例来说,此前有研究显示TPH2基因上的突变,与忧郁、双相情感障碍 BPD 和其他精神健康问题有关。而 5-HTT 基因上的突变,会减少负责在神经突触回收 5-羟色胺的蛋白。这些突变所产生的等位基因,被认为增加了大脑对外部风险的敏感性。
研究人员指出,这些基因的“敏感化”突变为家庭条件好的儿童提供了保护,同时对家庭条件差的儿童造成更大的端粒损伤。而那些缺乏上述等位基因的儿童,不论生活环境如何,端粒长度都没有什么差异。
研究显示,携带两个以上敏感化等位基因的男孩,会受到家庭环境的强烈影响。在紧张的家庭条件下产生最短的端粒,在较好的环境中产生最长的端粒。此前人们只知道这些突变影响了大脑的压力应答,但并未将其与端粒长度联系起来, Notterman 说。
下一步,研究团队打算将这项研究拓展到约 2500 名儿童和他们的母亲,以便对上述初步结论进行检验。鉴于环境影响在儿童 9 岁时就已出现, Notterman 认为,早期介入性措施也许可以帮助缓和逆境对儿童健康的影响。
Epel 表示:“这是理解社会差异如何影响生命健康的重要一步。”

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

PNAS

0 Following 4 Fans 0 Projects 58 Articles

SIMILAR ARTICLES

AbstractIn animal communication research, vocal labeling refers to incidents in which an animal consistently uses a specific acoustic signal when prese

Read More

AbstractWe show that easily accessible digital records of behavior, Facebook Likes, can be used to automatically and accurately predict a range of high

Read More

意义2010年 墨西哥湾北部深水地平线(MC252)灾难泄漏了超过400万桶原油。石油从海底架上升到了有许多大型中上层鱼类产卵的表层。在此我们描述了现场采集油样对包括蓝鳍金枪鱼,黄鳍金枪鱼和琥珀鱼在内的温水掠食动物迅速发育胚胎的影响。对于每个物种,环境相关MC252原油泄漏造成了心脏发育的严重缺陷。此

Read More

Abstract In the last decade there has been an exponential increase in knowledge about the genetic basis of complex human traits, including neuropsychi

Read More

AbstractGold mining has rapidly increased in western Amazonia, but the rates and ecological impacts of mining remain poorly known and potentially under

Read More

Abstract The interrelationships between hydrologically driven evolution of legacy landscapes downstream of major mining districts and the contaminatio

Read More

Abstract Changes in global (ocean and land) precipitation are among the most important and least well-understood consequences of climate change. Incre

Read More

AbstractAntiangiogenic therapy has shown clear activity and improved survival benefit for certain tumor types. However, an incomplete understanding of

Read More

AbstractThe biological mechanisms underlying long-term partner bonds in humans are unclear. The evolutionarily conserved neuropeptide oxytocin (OXT) is

Read More

Abstract Wine grapes present a unique biogeography model, wherein microbial biodiversity patterns across viticultural zones not only answer questions

Read More