The most important genes associated with a risk of developing type-2 diabetes have been identified, scientists report in a new study.
The research, published online 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 diabetes mellitus type 2, commonly known as type-2 diabetes.
The researchers identified four loci, or points on individuals’ genetic maps, which corresponded to a risk of developing the disorder. The scientists, from Imperial College London, McGill University, Canada, and other international institutions, believe their findings explain up to 70% of the genetic background of type-2 diabetes.
In addition, one of the genetic mutations which they detected might further explain the causes behind type-2 diabetes, potentially leading to new treatments. The research revealed that people with type-2 diabetes have a mutation in a particular zinc transporter known as SLC30A8, which is involved in regulating insulin secretion. 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.
Professor Philippe Froguel, one of the authors of the study from the Division of Medicine at Imperial College London, said: “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.”
The scientists reached their conclusions after comparing the genetic makeup of 700 people with type-2 diabetes and a family history of the condition, with 700 controls. They looked at mutations in the building blocks, called nucleotides, which make up DNA.
There are mutations in around one in every 600 nucleotides and the scientists examined over 392,000 of these mutations to find the ones specific to type-2 diabetes. The mutations are known as single-nucleotide polymorphisms.
The researchers confirmed their findings by analysing the genetic makeup of a further 5,000 individuals with type-2 diabetes and a family history of the disorder, to verify that the same genetic mutations were visible in these individuals.
Professor David Balding, co-author on the study from Imperial’s Division of Epidemiology, Public Health and Primary Care, said: "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.
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“A genome-wide association study identifies novel risk loci for type 2 diabetes” Nature, 11 February 2007, DOI 10.1038/nature05616
Robert Sladek1,2,4, Ghislain Rocheleau1*, Johan Rung4*, Christian Dina5*, Lishuang Shen1, David Serre1, Philippe Boutin5, Daniel Vincent4, Alexandre Belisle4, Samy Hadjadj6, Beverley Balkau7, Barbara Heude7, Guillaume Charpentier8, Thomas J. Hudson4,9, Alexandre Montpetit4, Alexey V. Pshezhetsky10, Marc Prentki10,11, Barry I. Posner2,12, David J. Balding13, David Meyre5, Constantin Polychronakos1,3 & Philippe Froguel5,14
(1)Departments of Human Genetics, (2)Medicine and (3)Pediatrics, Faculty of Medicine, McGill University, Canada.
(4)McGill University and Genome Quebec Innovation Centre, Canada.
(5)CNRS 8090-Institute of Biology, Pasteur Institute, France.
(6)Endocrinology and Diabetology, University Hospital, Poitiers, France (7)INSERM U780-IFR69, France.
(8)Endocrinology-Diabetology Unit, Corbeil-Essonnes Hospital, France.
(9)Ontario Institute for Cancer Research, Canada.
(10)Montreal Diabetes Research Center, Canada.
(11)Molecular Nutrition Unit and the Department of Nutrition, Canada.
(12)Polypeptide Hormone Laboratory and Department of Anatomy and Cell Biology, Canada.
(13)Department of Epidemiology & Public Health, Imperial College London, UK
(14)Section of Genomic Medicine, Imperial College London, UK.
*These authors contributed equally to this work.