An effort to scan the entire genetic code has made a major advance in understanding this common disease, reports Roger Highfield
A major advance in diagnosing people at risk of the most common form of diabetes is reported today by an international team of scientists that has scanned the entire human genetic makeup for clues.
The most important genes associated with a risk of developing type-2 diabetes have been identified, not only marking a major advance for diagnosis but pointing towards new forms of treatment for a disease that can cause complications such as blindness, heart disease, kidney problems, nerve damage and erectile dysfunction.
The research, published in Nature, is the first time the genetic makeup of any disease has been mapped in such detail. It should enable scientists to develop a genetic test to show an individual their likelihood of developing adult onset diabetes, commonly known as type-2 diabetes, and understand the way our diet and genes conspire to cause the disease, which affects three in every 100 peopl over 40 and 10 in every 100 over the age of 65.
The researchers identified four loci, or points on individuals' genetic maps, which corresponded to a risk of developing the disorder. Most remarkably, the scientists, from Imperial College London, McGill University, Canada, and other international institutions, believe their findings explain up to 70 per cent of the population's risk of type-2 diabetes.
In addition, one of the genetic mutations which they detected might further explain the causes of type-2 diabetes, potentially leading to new treatments.
The scientists reached their conclusions after comparing the genetic makeup of 700 people with type-2 diabetes and a family history of the condition, comparing them with 700 controls and searching for spelling mistakes in the genetic code linked with the disease. The researchers confirmed their findings in an additional 2,500 people with type-2 diabetes and an equal number of healthy controls, to verify that the same genetic mutations were linked.
The research revealed that people with diabetes have a mutation in a gene responsible for the manufacture in the body of a protein called SLC30A8, which is involved in regulating the secretion of insulin, the hormone that is central to diabetes.
The protein is a so called zinc transporter, one which plays a role in moving zinc from the blood into pancreas cells, where it is used to help make insulin. Because Type-2 diabetes is associated with a deficiency in insulin and the researchers believe it may be possible to treat it by fixing this transporter.
Prof Constantin Polychronakos of McGill University said that "this will definitely focus attention on the question of zinc in diabetes. It may be that zinc deficiency plays a role, in which case eating shellfish - a source of zinc - may be beneficial."
However, he stressed that it could be thaT the zinc transporter is underactive, in which case "loading the whole body with zinc may not be a good idea. A better idea might be to develop a drug that gives the transporter a boost." Prof Philippe Froguel of Imperial commented on the implications for diagnosis: "The two major reasons why people develop type-2 diabetes are obesity and a family link. Our new findings mean that we can create a good genetic test to predict people's risk of developing this type of diabetes.
"If we can tell someone that their genetics mean they are pre-disposed towards type-2 diabetes, they will be much more motivated to change things such as their diet to reduce their chances of developing the disorder. We can also use what we know about the specific genetic mutations associated with type-2 diabetes to develop better treatments."
Professor David Balding, co-author, added: "Until now, progress in understanding how genes influence disease has been painfully slow. This study is one of the first large studies to report results using the new genome-wide technology that governments and research charities have invested heavily in during the past few years. Our research shows that this technology can generate big leaps forward.
"The task now is to study the genes identified in our work more intensively, to understand more fully the disease processes involved, devise therapies for those affected and to try to prevent future cases," he added.
This work was funded by Genome Canada, Genome Quebec, and the Canada Foundation for Innovation. Cohort recruitment was supported by the Association Francaise des Diabetiques, INSERM, CNAMTS, Centre Hospitalier Universitaire Poitiers, La Fondation de France and industrial partners.
