News and Events
New gene associated with diabetes risk suggests link with body clock
8th December 2008
A connection between the body clock and abnormalities in metabolism and diabetes has been suggested in new research by an international team involving the MRC Epidemiology Unit in Cambridge, the University of Oxford, and the Wellcome Trust Sanger Institute.
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.
"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."
Professor Mark McCarthy, Oxford Centre for Diabetes, Endocrinology and Metabolism at the University of Oxford
Melatonin is a hormone that is strongly tied to the 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. By 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. The researchers suggest that the action of melatonin on the pancreas is probably being disturbed in this case.
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 an average rise of 0.07 mmol/l in fasting glucose level 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."
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. 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."
Dr Inês Barroso, Wellcome Trust Sanger Institute
The findings described in this article are taken from the following publication:
Prokopenko I, Langenberg C, Florez JC, Saxena R, Soranzo N, Thorleifsson G, Boehnke M, Barroso I, van Duijn C, Dupuis J, Watanabe RM, Stefánsson K, McCarthy MI, Wareham NJ, Meigs JB, Abecasis GR for the MAGIC investigators. Variants in the melatonin receptor 1B gene (MTNR1B) influence fasting glucose levels. Nature Genetics 2008. Published online in advance of print.
doi:http://www.nature.com/ng/journal/vaop/ncurrent/abs/ng.290.html
