The contribution of genetic factors to inter-individual variability in dietary isoflavone absorption and metabolism

遗传因素对膳食异黄酮吸收和代谢个体间差异的影响

• 批准号: BB/E007457/1
• 负责人: Dianne Ford
• 金额: $ 39.66万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE007457%2F1
• 关键词: contribution; genetic; factors; inter; individual

Lower incidence of some diseases, including cancer and cardiovascular disease, in populations who consume diets with a high content of soyabean products may be due to components of the soyabean known as isoflavones. Studies demonstrating biological activity of soyabean and soyabean extracts and isolated isoflavones in animal models and cultured cells provide evidence consistent with population-based studies that indicate such protective effects. Studies examining how individual subjects absorb and metabolise soyabean isoflavones reveal considerable variability between different individuals, and this variability is likely to determine the degree to which consumption of a soyabean-rich diet may offer health benefits to particular individuals. To be able to give informed advice on the potential beneficial effects of a soyabean-rich diet, or of taking isoflavone supplements, therefore, it is essential to understand factors that determine why different individials differ in their handling of dietary isoflavones. One major source of variability is likely to be differences in individuals' genetic make up with respect to the transporter proteins involved in the absorption of the isoflavones across the intestine and in enzymes responsible for metabolism of the isoflavones once absorbed. The aim of this project, therefore, is to study how specific genetic differences between individuals may affect the efficiency of absorption and the metabolism of isoflavones taken as a single oral dose. Subjects will be 150 healthy, premenopausal, Caucasian females selected from an initial group of 300 screened using DNA prepared from blood samples to obtain a sample group who vary with respect to differences in the genes we wish to study. The use of this restricted population group will limit variability in isoflavone absorption and metabolism resulting from non-genetic factors or from genetic differences additional to those we will study. Volunteers will collect all urine for 24 hours following the ingestion of capsules containing soyabean concentrate and will also give a blood sample 3 hours after taking the supplement. Isoflavone concentrations will be measured in these samples to indicate the efficiency of absorption and metabolism. There is evidence to indicate that some metabolism of the isoflavones takes place in the mouth and may be particularly important in terms of protection against oral cancer. We will also, therefore, investigate if there is any relationship between variability in some of the genes we will study that are related to this form of metabolic activity and rates of metabolism of a marker compound by extracts prepared from cells collected form the epithelial surface of the mouth by all volunteers. A link between genetic variability between individuals at specific locations in the DNA sequence and efficiency of isoflavone absorption and metabolism, should this be established, will add to a body of accumulating data concerning interindividual beneficial effects of dietary isoflavone intake and will have important implications for the design of future studies aimed at determining how genetic variability affects the influence of dietary isoflavones on markers of disease risk.

在食用大豆制品含量高的饮食的人群中，包括癌症和心血管疾病在内的一些疾病的发病率较低，这可能是由于大豆中被称为大豆酮的成分。在动物模型和培养细胞中进行的证明大豆和大豆提取物及分离的大豆异黄酮的生物活性的研究提供的证据与表明这种保护作用的基于人群的研究一致。研究个体受试者如何吸收和代谢大豆异黄酮的研究显示，不同个体之间存在相当大的差异，这种差异可能会决定食用富含大豆的饮食对特定个体的健康益处的程度。因此，为了能够就富含大豆的饮食或服用维生素补充剂的潜在有益效果提供明智的建议，必须了解决定为什么不同个体在处理膳食维生素D方面存在差异的因素。变异性的一个主要来源可能是个体遗传组成的差异，这些遗传组成涉及通过肠道吸收异黄酮的转运蛋白和一旦吸收后负责代谢异黄酮的酶。因此，该项目的目的是研究个体之间的特定遗传差异如何影响单次口服剂量的甘草酮的吸收和代谢效率。受试者将是150名健康的绝经前白人女性，从使用从血液样品制备的DNA筛选的300名初始组中选择，以获得关于我们希望研究的基因差异而变化的样品组。使用这个受限制的人群将限制非遗传因素或我们将研究的遗传差异导致的吸收和代谢的变异性。志愿者将在摄入含有大豆浓缩物的胶囊后24小时内收集所有尿液，并在服用补充剂3小时后提供血液样本。将测量这些样品中的异黄酮浓度，以指示吸收和代谢的效率。有证据表明，一些代谢的β-羟考酮发生在口腔中，可能是特别重要的保护口腔癌。因此，我们还将研究与这种形式的代谢活性相关的一些基因的变异性与标记化合物的代谢率之间是否存在任何关系，所述标记化合物是通过从所有志愿者的口腔上皮表面收集的细胞制备的提取物来进行研究的。DNA序列中特定位置的个体之间的遗传变异性与吸收和代谢效率之间的联系，如果这一点得到确立，这将增加一个关于饮食中β-胡萝卜素摄入的个体间有益影响的积累数据的主体，并将对未来旨在确定遗传变异性如何影响饮食中β-胡萝卜素对以下标志物的影响的研究设计产生重要影响：疾病风险。

项目成果

Could Sirt1-mediated epigenetic effects contribute to the longevity response to dietary restriction and be mimicked by other dietary interventions?

Sirt1 介导的表观遗传效应是否有助于对饮食限制的长寿反应，并被其他饮食干预措施模仿？

• DOI: 10.1007/s11357-009-9104-5
• 发表时间: 2009
• 期刊: Age (Dordrecht, Netherlands)
• 作者: Wakeling LA

SIRT1 affects DNA methylation of polycomb group protein target genes, a hotspot of the epigenetic shift observed in ageing.

SIRT1影响Polycomb基团蛋白靶基因的DNA甲基化，这是衰老中观察到的表观遗传转移的热点。

• DOI: 10.1186/s40246-015-0036-0
• 发表时间: 2015-06-24
• 期刊: Human genomics
• 影响因子: 4.5
• 作者: Wakeling LA;Ions LJ;Escolme SM;Cockell SJ;Su T;Dey M;Hampton EV;Jenkins G;Wainwright LJ;McKay JA;Ford D
• 通讯作者: Ford D