Messenger RNA analysis of genes implicated in susceptibility to type 2 diabetes.

对与 2 型糖尿病易感性相关的基因进行信使 RNA 分析。

• 批准号: MR/J006777/1
• 负责人: Lorna Harries
• 金额: $ 40.98万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ006777%2F1
• 关键词: Messenger; RNA; analysis; genes; implicated

We are now facing an epidemic of type 2 diabetes (T2D). This disease, which used to be found only in the middle aged, is increasingly now being seen in much younger people because of rising levels of obesity, lack of exercise and other risk factors. We are beginning to understand, however, why some people are more likely to get T2D, whilst others do not. Everybody's genes are slightly different. We all carry large numbers of very small changes in our genes and some of these changes may make people carrying them slightly more susceptible to diabetes or other diseases. Over the past decade, we have found over 40 changes that make people more likely to become diabetic. We now face an important task to find out exactly how these changes cause diabetes. Most of the changes identified have been in regions of the genes that control whether genes are switched on or switched off. All cells contain all the genes, but not all are switched on in every cell type. When a gene is switched on, it produces a message, which tells the cell to make a particular protein, which may be necessary in the control of blood sugar, or in other bodily processes. Most genes can also make more than one type of message. The amount or nature of these messages is important to keep our cells healthy and to make our bodies function. These small changes in the genes could cause genes to be switched off when they should be switched on, or vice versa. They could also cause the genes to make the wrong sort of messages, or the right messages but at the wrong time. All of these possibilities could contribute to the development of diabetes. In this study, I aim to find out whether the changes in the genes that are associated with T2D affect the amount or number of messages made, and how this could then predispose to diabetes.

我们现在面临着2型糖尿病（T2D）的流行。这种疾病过去只在中年人身上发现，现在越来越多地出现在年轻人身上，原因是肥胖水平上升、缺乏锻炼和其他风险因素。然而，我们开始明白，为什么有些人更容易得T2D，而另一些人却不会。每个人的基因都略有不同。我们的基因都携带着大量非常微小的变化，其中一些变化可能会使携带这些基因的人更容易患糖尿病或其他疾病。在过去的十年里，我们发现了40多种使人们更容易患糖尿病的变化。我们现在面临着一项重要的任务，即找出这些变化究竟是如何导致糖尿病的。大多数已发现的变化都发生在控制基因开启或关闭的基因区域。所有的细胞都包含所有的基因，但并不是所有的细胞类型都被激活。当一个基因被激活时，它会产生一条信息，告诉细胞制造一种特定的蛋白质，这种蛋白质可能是控制血糖或其他身体过程所必需的。大多数基因也可以产生不止一种类型的信息。这些信息的数量或性质对保持我们的细胞健康和使我们的身体功能很重要。这些基因上的微小变化可能导致基因在应该开启时被关闭，反之亦然。它们也可能导致基因产生错误的信息，或者在错误的时间产生正确的信息。所有这些可能性都可能导致糖尿病的发展。在这项研究中，我的目标是找出与T2D相关的基因的变化是否会影响产生的信息的数量，以及这是如何使糖尿病易感性的。

项目成果

The Common HNF1A Variant I27L Is a Modifier of Age at Diabetes Diagnosis in Individuals With HNF1A-MODY.

• DOI: 10.2337/db18-0133
• 发表时间: 2018-09
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: Locke JM;Saint-Martin C;Laver TW;Patel KA;Wood AR;Sharp SA;Ellard S;Bellanné-Chantelot C;Hattersley AT;Harries LW;Weedon MN
• 通讯作者: Weedon MN

Peripheral Blood Transcriptomic Signatures of Fasting Glucose and Insulin Concentrations.

• DOI: 10.2337/db16-0470
• 发表时间: 2016-12
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: Chen BH;Hivert MF;Peters MJ;Pilling LC;Hogan JD;Pham LM;Harries LW;Fox CS;Bandinelli S;Dehghan A;Hernandez DG;Hofman A;Hong J;Joehanes R;Johnson AD;Munson PJ;Rybin DV;Singleton AB;Uitterlinden AG;Ying S;MAGIC Investigators;Melzer D;Levy D;van Meurs JB;Ferrucci L;Florez JC;Dupuis J;Meigs JB;Kolaczyk ED
• 通讯作者: Kolaczyk ED

A cautionary tale: the non-causal association between type 2 diabetes risk SNP, rs7756992, and levels of non-coding RNA, CDKAL1-v1.

• DOI: 10.1007/s00125-015-3508-9
• 发表时间: 2015-04
• 期刊: DIABETOLOGIA
• 影响因子: 8.2
• 作者: Locke, Jonathan M.;Wei, Fan-Yan;Tomizawa, Kazuhito;Weedon, Michael N.;Harries, Lorna W.
• 通讯作者: Harries, Lorna W.