Public Release:  Discovery of new gene associated with diabetes risk suggests link with body clock

Wellcome Trust Sanger Institute

A connection between the body clock and abnormalities in metabolism and diabetes has been suggested in new research by an international team involving the University of Oxford, the Wellcome Trust Sanger Institute and the MRC Epidemiology Unit in Cambridge.

The researchers have identified a gene involved in the way the body responds to the 24 hour day-night cycle that is strongly linked to high blood sugar levels and an increased risk of type 2 diabetes. The results of the genome-wide association scan are published in Nature Genetics.

"We have extremely strong, incontrovertible evidence that the gene encoding melatonin receptor 1B is associated with high fasting glucose levels and increased risk of type 2 diabetes," says Professor Mark McCarthy of the Oxford Centre for Diabetes, Endocrinology and Metabolism at the University of Oxford.

Melatonin is a hormone that is strongly tied to control of our sleep-wake cycles, with concentrations in the blood peaking at night-time and dipping during the day. As a result, melatonin is implicated in conditions like jetlag and sleep disorders.

Disrupted sleep patterns are known to be associated with a range of health problems including metabolic disorders like diabetes, but it is not understood how they are connected. In identifying a link between a melatonin receptor and blood sugar levels, this study provides genetic evidence that mechanisms controlled by our body clock are connected to the machinery that keeps us metabolically healthy. It seems likely that the action of melatonin on the pancreas is being disturbed in this case, the researchers suggest.

The international research collaboration combined ten genome-wide association scans involving a total of over 36,000 individuals of European descent. A variant in the gene encoding melatonin receptor 1B (MTNR1B) showed a rise of 0.07 mmol/l in fasting glucose level on average and a 9% increase in risk of type 2 diabetes for each copy of the gene variant inherited from a parent.

"High fasting glucose levels are early markers of diabetes and this observation provides important clues about the possible mechanisms linking genes to diabetes risk," says Professor Nick Wareham, Director of the MRC Epidemiology Unit in Cambridge.

Other genes have previously been shown to be associated with high blood sugar levels, but have not shown an increase in diabetes risk. The melatonin receptor found in this genome-wide study is the first gene to be linked to both high blood sugar and increased risk of diabetes.

"Although levels of glucose in the blood are used to diagnose diabetes, most of the genes previously associated with high glucose levels do not increase risk of diabetes," says Dr Inês Barroso from the Wellcome Trust Sanger Institute. "We have found a variant - a G in the genome in place of a C - in MTNR1B. This single-letter change influences both sugar levels and diabetes. This remarkable result should allow us to gain new insight into this problem."

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Notes to Editors

1. Contact details

For more information please contact Mark McCarthy at the Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University on +44 (0)7825 344066 or mark.mccarthy@drl.ox.ac.uk
or the Press Office, University of Oxford on +44 (0)1865 280530 or press.office@admin.ox.ac.uk.

2. Publication details

Prokopenko I et al. (2008) Variants in MTNR1B influence fasting glucose levels. Nature Genetics. Published online in advance of print doi:http://dx.doi.org/10.1038/ng.290

3. Type 2 diabetes is the most common type of diabetes and accounts for 85-95 per cent of cases. It tends to affect people later in life and develops when the body doesn't make enough insulin or becomes insulin resistant. The condition runs strongly in families, so there has long been a suspicion that genes are involved in susceptibility to diabetes. Close to 20 genes have now been associated with the condition. According to Diabetes UK, there are currently over 2.5 million people with diabetes in the UK and there are more than half a million people with diabetes who have the condition and don't know it.

4. Affiliated Institutions

Oxford University's Medical Sciences Division is one of the largest biomedical research centres in Europe. It represents almost one-third of Oxford University's income and expenditure, and two-thirds of its external research income. Oxford's world-renowned global health programme is a leader in the fight against infectious diseases (such as malaria, HIV/AIDS, tuberculosis and avian flu) and other prevalent diseases (such as cancer, stroke, heart disease and diabetes). Key to its success is a long-standing network of dedicated Wellcome Trust-funded research units in Asia (Thailand, Laos and Vietnam) and Kenya, and work at the MRC Unit in The Gambia. Long-term studies of patients around the world are supported by basic science at Oxford and have led to many exciting developments, including potential vaccines for tuberculosis, malaria and HIV, which are in clinical trials.

http://www.medsci.ox.ac.uk

The Medical Research Council supports the best scientific research to improve human health. Its work ranges from molecular level science to public health medicine and has led to pioneering discoveries in our understanding of the human body and the diseases which affect us all.

http://www.mrc.ac.uk

MRC Epidemiology Unit: The goal of the MRC Epidemiology Unit is to study the genetic, development and environmental determinants of obesity, diabetes and related metabolic disorders and to contribute to the scientific basis of prevention.

www.mrc-epid.cam.ac.uk

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992 as the focus for UK sequencing efforts. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms such as mouse and zebrafish, and more than 90 pathogen genomes. In October 2005, new funding was awarded by the Wellcome Trust to enable the Institute to build on its world-class scientific achievements and exploit the wealth of genome data now available to answer important questions about health and disease. These programmes are built around a Faculty of more than 30 senior researchers. The Wellcome Trust Sanger Institute is based in Hinxton, Cambridge, UK.

http://www.sanger.ac.uk

The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £650 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.

http://www.wellcome.ac.uk

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