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release date: 29-Jan-2012
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Contact: Sam Wong
sam.wong@imperial.ac.uk
44-207-594-2198
Imperial College
London

A study published in Nature Genetics today has found new
evidence for a link between the body clock hormone melatonin
and type 2 diabetes. The study found that people who carry rare
genetic mutations in the receptor for melatonin have a much
higher risk of type 2 diabetes.

The findings should help scientists to more accurately assess
personal diabetes risk and could lead to the development of
personalised treatments.

Previous research has found that people who work night shifts
have a higher risk of type 2 diabetes and heart disease.
Studies have also found that if volunteers have their sleep
disrupted repeatedly for three days, they temporarily develop
symptoms of diabetes.

The body's sleep-wake cycle is controlled by the hormone
melatonin, which has effects including drowsiness and lowering
body temperature. In 2008, a genetic study led by Imperial
College London discovered that people with common variations in
the gene for MT2, a receptor for melatonin, have a slightly
higher risk of type 2 diabetes.

The new study reveals that carrying any of four rare mutations
in the MT2 gene increases a person's risk of developing type 2
diabetes six times. The release of insulin, which regulates
blood sugar levels, is known to be regulated by melatonin. The
researchers suggest that mutations in the MT2 gene may disrupt
the link between the body clock and insulin release, leading to
abnormal control of blood sugar.

Professor Philippe Froguel, from the School of Public Health at
Imperial College London, who led the study, said: "Blood sugar
control is one of the many processes regulated by the body's
biological clock. This study adds to our understanding of how
the gene that carries the blueprint for a key component in the
clock can influence people's risk of diabetes.

"We found very rare variants of the MT2 gene that have a much
larger effect than more common variants discovered before.
Although each mutation is rare, they are common in the sense
that everyone has a lot of very rare mutations in their DNA.
Cataloguing these mutations will enable us to much more
accurately assess a person's risk of disease based on their
genetics."

In the study, the Imperial team and their collaborators at
several institutions in the UK and France examined the MT2 gene
in 7,632 people to look for more unusual variants that have a
bigger effect on disease risk. They found 40 variants
associated with type 2 diabetes, four of which were very rare
and rendered the receptor completely incapable of responding to
melatonin. The scientists then confirmed the link with these
four variants in an additional sample of 11,854 people.

Professor Froguel and his team analysed each mutation by
testing what effect they have on the MT2 receptor in human
cells in the lab. The mutations that completely prevented the
receptor from working proved to have a very big effect on
diabetes risk, suggesting that there is a direct link between
MT2 and the disease.

###

The research was funded by the Wellcome Trust, the National
Institute for Health Research and the Medical Research Council
in the UK and the Agence National de la Recherche, the Contrat
de Projets Etat-R?gion Nord-Pas-De-Calais, the Soci?t?
Francophone du Diab?te, the Fondation Recherche M?dicale and
the Centre National de la Recherche Scientifique in France.

For further information please contact:

Sam Wong
Research Media Officer
Imperial College London
Email: sam.wong@imperial.ac.uk
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248

Notes to editors:

1. Journal reference
A. Bonnefond et al. 'Rare MTNR1B variants impairing melatonin
receptor 1B function contribute to type 2 diabetes' Nature
Genetics, published online 29 January 2012.

2. About Imperial College London

Consistently rated amongst the world's best universities,
Imperial College London is a science-based institution with a
reputation for excellence in teaching and research that
attracts 14,000 students and 6,000 staff of the highest
international quality. Innovative research at the College
explores the interface between science, medicine, engineering
and business, delivering practical solutions that improve
quality of life and the environment - underpinned by a dynamic
enterprise culture.

Since its foundation in 1907, Imperial's contributions to
society have included the discovery of penicillin, the
development of holography and the foundations of fibre optics.
This commitment to the application of research for the benefit
of all continues today, with current focuses including
interdisciplinary collaborations to improve global health,
tackle climate change, develop sustainable sources of energy
and address security challenges.

In 2007, Imperial College London and Imperial College
Healthcare NHS Trust formed the UK's first Academic Health
Science Centre. This unique partnership aims to improve the
quality of life of patients and populations by taking new
discoveries and translating them into new therapies as quickly
as possible.

Website: http://www.imperial.ac.uk
Twitter: http://www.twitter.com/imperialspark
Podcast: http://www.imperial.ac.uk/media/podcasts

3. About the Medical Research Council

For almost 100 years the Medical Research Council has improved
the health of people in the UK and around the world by
supporting the highest quality science. The MRC invests in
world-class scientists. It has produced 29 Nobel Prize winners
and sustains a flourishing environment for internationally
recognised research. The MRC focuses on making an impact and
provides the financial muscle and scientific expertise behind
medical breakthroughs, including one of the first antibiotics
penicillin, the structure of DNA and the lethal link between
smoking and cancer. Today MRC funded scientists tackle research
into the major health challenges of the 21st century. http://www.mrc.ac.uk

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Read more:
Body clock receptor linked to diabetes in new genetic study

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