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, 80 per cent of the risk of cardiovascular disease is related to a blood glucose level just above the average and high blood glucose levels in otherwise healthy people often are indications of heart disease and higher mortality rates. The research was conducted by Dr. Phillippe Froguel and Dr. Robert Sladek, Dr. Constantin Polychronakos and their teams at McGill University. 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, "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. "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.
The results were published May 1 in the online version of the journal Science.