高血糖已可以用基因学解释
　　加拿大、法国及英国的研究人员们找到了一组能够决定人们血糖水平高低的DNA序列。这是一个具有巨大应用前景的发现，因为健康人血糖水平增高通常提示有心脏病或者较高的死亡率。研究的结果发表在五月一日《科学》杂志的在线版上。

　　这项研究是由Phillippe Froguel博士和他在伦敦帝国学院、法国里尔德le Centre national de la recherche scientifique (CNRS) 的同事，连同Robert Sladek博士, Constantin Polychronakos博士以及他们位于蒙特利尔的McGill大学、McGill大学健康中心的同事们一起合作进行的。Sladek博士实验室的博士后Ghislain Rocheleau是这项研究的第一共同作者。

　　在这项研究中，科学家们对一个糖尿病大型基因组研究项目所搜集的数据进行了分析，这些数据来自于390，000个不同地域或所在地的人类基因组。研究的第一个有关糖尿病的重要发现发表于2007年，并受到了世界媒体的关注。

　　在这个项目中，科研人员主要针对的是血糖水平正常的非糖尿病健康人的基因。他们发现三个不同基因中的某一个单一DNA突变可以部分解释人们血糖水平又高有低的原因。研究人员相信这些基因实际上主要影响的是血液中葡萄糖阈水平的高低，而葡萄糖的阈水平则决定了胰岛素何时分泌。个体的血糖阈值越高，则引发胰岛素分泌的血糖水平也就越高。

　　“这些基因序列可以为我们解释5%的健康人血糖水平的正常变异，” Sladek博士说，“5%听起来也许不是很大，但相对于比较复杂的特征来说，就已经显得非常可观了。比如，人的身高就是由上百个不同的基因所控制的。”

　　这些发现使人们对葡糖糖代谢的基因发生机制的认识又向前推进了一大步，研究人员称，他们还相信这还将有助于人们在基因层面上更加深入地了解代谢性疾病的产生原因。 “从理论上说，所有包含基因操作的医学实验都能应用这种方案，“Sladek解释说。“这就可以给我们带来一种‘个体化医疗’的概念。最终，我们也许有望根据每个人不同的基因结构来为他们订制各自的治疗方案。”

　　高血糖水平同样也是和心血管疾病紧密相连的——这一发现为新的管理方案和治疗方法的发展提供了可能。“认识到这点很重要，即：高血糖水平，即使是在正常或非糖尿病的范围之内的也是导致早期死亡的危险因素之一。”伦敦帝国学院的Philippe Froguel博士说。“流行病学研究显示心血管疾病80%的危险性都是和稍高于正常的血糖水平相关联的。”

　　“很显现，我们下一步要做的就是要找一些心脏病方面的合作者，然后看看这些基因能不能在治疗心脏病方面发挥作用，”Sladek博士又说。

　　“我们为这些发现而倍感自豪，因为这又一次充分证明了魁北克科学家们的杰出才华，”魁北克基因组的总裁及CEO说，“这些发现是由魁北克基因组资助的项目所带来的直接成果，它清楚地显示出在寻找改善人类健康的方法中基因组学所起到的战略性作用。我们还想要强调一下各个研究所之间的合作，因为正是这种合作才促使了这种进步的实现。祝贺你和你的团队，Sladek博士！”

Dangerously High Blood Glucose Levels Explained By Genetic Breakthrough

Canadian, French and British researchers have identified a DNA sequence that controls the variability of blood glucose levels in people. This is a potentially significant discovery because high blood glucose levels in otherwise healthy people often are indications of heart disease and higher mortality rates. The results were published May 1 in the online version of the journal Science.

The research was conducted by Dr. Phillippe Froguel and colleagues at Imperial College London and le Centre national de la recherche scientifique (CNRS) in Lille, France, in collaboration with Dr. Robert Sladek, Dr. Constantin Polychronakos and their teams at McGill University and the McGill University Health Centre (MUHC) in Montreal. Dr. Ghislain Rocheleau, a post-doctoral fellow in Dr. Sladek's lab, is the study's co-first author.

The scientists worked with data collected from a large genome study originally conducted for diabetes research that looked at over 390,000 different locations - or loci - on the human genome. The study's first important diabetes results were published in 2007 and received worldwide media attention.

In this study, researchers looked at the genetic code of healthy, non-diabetic individuals whose blood glucose levels were in the normal range. They discovered that a single DNA mutation within three different genes explained, in part, why some individuals have high or low blood glucose levels. The researchers believe that these genes actually affect the threshold level of glucose in the bloodstream, which triggers the secretion of insulin. The higher the threshold, the higher the blood glucose level will rise before insulin starts to regulate it.

"These sequences explain about 5 per cent of the normal variation in blood glucose levels between otherwise healthy people," explained Dr. Sladek, of McGill's Faculty of Medicine, the Department of Human Genetics, the MUHC Research Institute and the McGill University and Génome Québec Innovation Centre. "Five per cent may not sound huge, but for complex traits, that's rather a lot. By contrast, hundreds of different genes influence height."

These findings provide important insights into the genetic mechanisms behind glucose metabolism, say the researchers, which they predict will lead to greater understanding of the genetic roots of metabolic disorders in general. "In theory, any medical test which has a genetic component can use this approach," Sladek explained. "That brings us to the idea of 'personalized medicine.' Eventually, we might be able to customize treatment to an individual's unique genetic structure."

High blood glucose levels are also closely linked with increased risk for cardiovascular disease, and these findings hold out of the hope of discovering new management techniques and treatments. "It's important to know that a high blood glucose level, even within the normal and non-diabetic range, is a risk factor for early mortality," explains Dr. Philippe Froguel of Imperial College and CNRS. "Epidemiological studies have shown that 80 per cent of the risk of cardiovascular disease is related to a blood glucose level just above the average."

"Obviously, the next step would be to get some collaborators on the heart disease side, and see whether some of these other genes might also play a role," added Dr. Sladek.

"We are proud of this announcement, which once again confirms the scientific excellence and talent of Québec's scientists," said Paul L'Archevêque, President and CEO of Génome Québec. "These findings, which are the direct result of studies co-financed by Génome Québec, clearly show the strategic role of genomics in the search for solutions to improve human health. We would also like to underline the cooperation among the institutes, an initiative that made this major advance possible. Congratulations to Dr. Sladek and his team!"