Does abnormal one-carbon metabolism or hyperglycaemia in utero cause epigenetic change and fetal programming of cardiome

子宫内一碳代谢异常或高血糖是否会导致表观遗传变化和胎儿心脏编程

• 批准号: G0800441/1
• 负责人: Sarah Finer
• 金额: $ 28.96万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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=G0800441%2F1
• 关键词: Does; abnormal; carbon; metabolism; hyperglycaemia

Diabetes and cardiovascular disease (the ‘cardiometabolic‘ diseases) are becoming increasingly common throughout the world. The risk of developing these diseases relates to both genetic inheritance and a person‘s environment. The effects of environment are particularly important during pregnancy, and studies of malnourished and diabetic mothers show an increased risk of cardiometabolic disease in their children. This idea of disease being ‘programmed‘ during fetal development has been studied across populations and in animal experiments, but the mechanisms through which it occurs are not understood. In this respect, the field of epigenetics is providing an exciting insight into how this programming might occur. It describes how environmental triggers can affect how genes are switched on or off via a sequence of chemical reactions around the structure of DNA. This study will look at how high blood glucose levels and poor nutrition in mothers could cause epigenetic changes that put offspring at risk of cardiometabolic disease. The study will be done in mice as well as humans to identify whether these changes can be inherited through generations. New techniques involving both laboratory experiments and computerised mathematical analysis will be used to answer these questions.

糖尿病和心血管疾病(心脏代谢性疾病)在全世界正变得越来越普遍。罹患这些疾病的风险既与遗传有关，也与人的环境有关。环境的影响在怀孕期间尤其重要，对营养不良和糖尿病母亲的研究表明，她们的孩子患心脏代谢性疾病的风险增加。这种疾病是在胎儿发育过程中被“编程”的想法已经在人群中和动物实验中进行了研究，但它发生的机制尚不清楚。在这方面，表观遗传学领域为这种编程可能如何发生提供了令人兴奋的洞察力。它描述了环境触发因素如何通过围绕DNA结构的一系列化学反应来影响基因的开启或关闭。这项研究将着眼于母亲的高血糖水平和营养不良如何导致表观遗传变化，从而使子女面临心脏代谢性疾病的风险。这项研究将在老鼠和人类身上进行，以确定这些变化是否可以世代相传。涉及实验室实验和计算机数学分析的新技术将被用来回答这些问题。