Nutrition and early life programming: exploring epigenetic mechanisms

营养和早期生命规划：探索表观遗传机制

• 批准号: BB/F007981/1
• 负责人: Caroline Relton
• 金额: $ 50.84万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF007981%2F1
• 关键词: Nutrition; early; life; programming; exploring

Nutritional stresses in early life have long-lasting effects on health. Rapid growth in early postnatal life has been linked to increased incidence of common diseases such as obesity, cardiovascular disease and type 2 diabetes in later life. The mechanisms that link early post-natal nutrition with later ill health have not been well defined. Infants born preterm are encouraged to gain weight rapidly but this has important implications for adult health. By studying children who were born preterm, now aged 10-12 years, who participated in a post-natal nutritional trial we can glean important information not only about the health consequences of different infant feeding regimen, but also about the molecular mechanisms involved. This project aims to examine the molecular mechanisms that allow early nutrition to be 'memorised' at a cellular level. The genome is 'marked' in response to nutritional exposures and these markings can induce stable changes in which genes are switched on and switched off. Epigenetics refers to the decoration of the genome by these chemical markings and is an emerging field of post-genomic science. New technologies will be used to study epigenetic markings and gene expression in 120 children born preterm. These children took part in a nutritional trial and were fed one of three different diets from 36 weeks gestation to 6 months of age. Their growth and development has been followed over the last 10-12 years. Changes observed in epigenetic status and in gene expression will be related to differences in the health of the children, such as body composition, blood pressure, glucose and insulin levels and levels of hormones involved in fat metabolism. This project will use new tools in biotechnology and bioinformatics to study how nutrition influences the genome and how this may have long lasting effects on health.

生命早期的营养压力对健康有长期的影响。出生后早期的快速增长与以后生活中常见疾病如肥胖、心血管疾病和2型糖尿病的发病率增加有关。将产后早期营养与后来的健康不良联系起来的机制尚未得到很好的界定。鼓励早产儿迅速增加体重，但这对成人健康有重要影响。通过研究早产儿，现在年龄在10-12岁，他们参加了产后营养试验，我们不仅可以收集关于不同婴儿喂养方案的健康后果的重要信息，而且还可以收集有关分子机制的重要信息。该项目旨在研究允许早期营养在细胞水平上“记忆”的分子机制。基因组是“标记”的营养暴露的反应，这些标记可以诱导稳定的变化，其中基因被打开和关闭。表观遗传学是指通过这些化学标记对基因组进行修饰，是后基因组科学的一个新兴领域。新技术将用于研究120名早产儿的表观遗传标记和基因表达。这些孩子参加了营养试验，从怀孕36周到6个月大，他们被喂食三种不同饮食中的一种。在过去10-12年里，一直在跟踪它们的成长和发展。观察到的表观遗传状态和基因表达的变化将与儿童健康的差异有关，如身体成分、血压、葡萄糖和胰岛素水平以及参与脂肪代谢的激素水平。该项目将使用生物技术和生物信息学的新工具来研究营养如何影响基因组，以及营养如何对健康产生长期影响。

项目成果

Bioinformatic interrogation of expression array data to identify nutritionally regulated genes potentially modulated by DNA methylation.

对表达阵列数据进行生物信息学询问，以识别可能受 DNA 甲基化调节的营养调节基因。

• DOI: 10.1007/s12263-008-0095-0
• 发表时间: 2008-12
• 期刊: GENES AND NUTRITION
• 影响因子: 3.5
• 作者: McKay, J. A.;Adriaens, M. E.;Ford, D.;Relton, C. L.;Evelo, C. T. A.;Mathers, J. C.
• 通讯作者: Mathers, J. C.

Postnatal growth and DNA methylation are associated with differential gene expression of the TACSTD2 gene and childhood fat mass.

• DOI: 10.2337/db11-1039
• 发表时间: 2012-02
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: Groom A;Potter C;Swan DC;Fatemifar G;Evans DM;Ring SM;Turcot V;Pearce MS;Embleton ND;Smith GD;Mathers JC;Relton CL
• 通讯作者: Relton CL

Genetic selection? A study of individual variation in the enzymes of folate metabolism.

• DOI: 10.1186/1471-2350-11-18
• 发表时间: 2010-02-01
• 期刊: BMC medical genetics
• 作者: Jennings BA;Willis GA;Skinner J;Relton CL
• 通讯作者: Relton CL

Genetic and non-genetic influences during pregnancy on infant global and site specific DNA methylation: role for folate gene variants and vitamin B12.

• DOI: 10.1371/journal.pone.0033290
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: McKay JA;Groom A;Potter C;Coneyworth LJ;Ford D;Mathers JC;Relton CL
• 通讯作者: Relton CL

Epigenetic epidemiology of common complex disease: prospects for prediction, prevention, and treatment.

• DOI: 10.1371/journal.pmed.1000356
• 发表时间: 2010-10-26
• 期刊: PLoS medicine
• 影响因子: 15.8
• 作者: Relton CL;Davey Smith G
• 通讯作者: Davey Smith G