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Genetic breakthrough explains dangerously high blood glucose levels

Published: 1 May 2008

Discovery brings promise of 鈥減ersonalized medicine鈥 closer to reality

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 will be 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 看片视频 University and the 看片视频 University Health Centre (MUHC) in Montreal. Dr. Ghislain Rocheleau, a post-doctoral fellow in Dr. Sladek鈥檚 lab, is the study鈥檚 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 鈥 or loci 鈥 on the human genome. The study鈥檚 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.

鈥淭hese sequences explain about 5 per cent of the normal variation in blood glucose levels between otherwise healthy people,鈥 explained Dr. Sladek, of 看片视频鈥檚 Faculty of Medicine, the Department of Human Genetics, the MUHC Research Institute and the 看片视频 University and G茅nome Qu茅bec Innovation Centre. 鈥淔ive per cent may not sound huge, but for complex traits, that鈥檚 rather a lot. By contrast, hundreds of different genes influence height.鈥

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. 鈥淚n theory, any medical test which has a genetic component can use this approach,鈥 Sladek explained. 鈥淭hat brings us to the idea of 鈥榩ersonalized medicine.鈥 Eventually, we might be able to customize treatment to an individual鈥檚 unique genetic structure.鈥

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. 鈥淚t鈥檚 important to know that a high blood glucose level, even within the normal and non-diabetic range, is a risk factor for early mortality,鈥 explains Dr. Philippe Froguel of Imperial College and CNRS. 鈥淓pidemiological studies have shown that 80 per cent of the risk of cardiovascular disease is related to a blood glucose level just above the average.鈥

鈥淥bviously, 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,鈥 added Dr. Sladek.

鈥淲e are proud of this announcement, which once again confirms the scientific excellence and talent of Qu茅bec鈥檚 scientists,鈥 said Paul L鈥橝rchev锚que, President and CEO of G茅nome Qu茅bec. 鈥淭hese findings, which are the direct result of studies co-financed by G茅nome Qu茅bec, 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!鈥

The 看片视频 University and G茅nome Qu茅bec Innovation Centre, situated on the 看片视频 campus, serves as a vast resource of knowledge and technology to the academic, industrial and commercial sectors. 鈥淭he Innovation Centre is a world-class research facility for genomics and proteomics,鈥 said Denis Th茅rien, Vice-Principal (Research and International Relations). 鈥淭his latest genetic breakthrough exemplifies the powerful potential of 看片视频鈥檚 scientific partnership with Genome Quebec and Genome Canada 鈥 a partnership that continues to create synergies and alliances that propel us forward on the world stage.鈥

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