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Last Updated: Oct 11, 2012 - 10:22:56 PM
Research Article
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Major genetic study identifies gene for obesity

Apr 14, 2007 - 3:35:51 AM , Reviewed by: Dr. Sanjukta Acharya
"The discovery of a gene that influences the development of obesity in the general population provides a new tool for understanding how some people appear to gain weight more easily than others."

Level of Evidence
3b - Individual Case-Control Study
Key Points of this article
The researchers identified a strong association between an increase in body mass index and a variation of the gene FTO.
The study found that people carrying one copy of the FTO allele have a 30 per cent increased risk of being obese compared to a person with no copies.
However, a person carrying two copies of the allele has a 70 per cent increased risk of being obese, being on average 3 kg heavier than a similar person with no copies.
Among white Europeans, approximately one in six people carries both copies of the allele.
 
Main results
People with two copies of a particular gene variant have a 70 per cent higher risk of being obese than those with no copies.
FTO gene
The FTO gene was first discovered whilst studying the DNA of a cohort of patients with type 2 diabetes. The risk of developing type 2 diabetes increases significantly for obese people. Through its effect on BMI, having one copy of the FTO allele increases the risk of developing type 2 diabetes by 25 per cent, having two by 50 per cent.
Epidemiology
Obesity is a major cause of disease, associated with an increased risk of type 2 diabetes, heart disease and cancer. It is typically measured using body mass index (BMI). As a result of reduced physical activity and increased food consumption, the prevalence of obesity is increasing worldwide. According to the 2001 Health Survey for England, over a fifth of males and a similar proportion of females aged 16 and over in England were classified as obese. Half of men and a third of women were classified as overweight.
[RxPG] Scientists have identified the most clear genetic link yet to obesity in the general population as part of a major study of diseases funded by the Wellcome Trust, the UK's largest medical research charity. People with two copies of a particular gene variant have a 70 per cent higher risk of being obese than those with no copies.

Obesity is a major cause of disease, associated with an increased risk of type 2 diabetes, heart disease and cancer. It is typically measured using body mass index (BMI). As a result of reduced physical activity and increased food consumption, the prevalence of obesity is increasing worldwide. According to the 2001 Health Survey for England, over a fifth of males and a similar proportion of females aged 16 and over in England were classified as obese. Half of men and a third of women were classified as overweight.

Scientists from the Peninsula Medical School, Exeter, and the University of Oxford first identified a genetic link to obesity through a genome-wide study of 2,000 people with type 2 diabetes and 3,000 controls. This study was part of the Wellcome Trust Case Control Consortium, one of the biggest projects ever undertaken to identify the genetic variations that may predispose people to or protect them from major diseases. Through this genome-wide study, the researchers identified a strong association between an increase in BMI and a variation, or "allele", of the gene FTO. Their findings are published online today in the journal Science.

The researchers then tested a further 37,000 samples for this gene from Bristol, Dundee and Exeter as well as a number of other regions in the UK and Finland. Bristol University’s ALSPAC study (also known as Children of the 90s), which has followed the development of 14,000 children since before birth, made a significant contribution to this work.

The study found that people carrying one copy of the FTO allele have a 30 per cent increased risk of being obese compared to a person with no copies. However, a person carrying two copies of the allele has a 70 per cent increased risk of being obese, being on average 3kg heavier than a similar person with no copies. Amongst white Europeans, approximately one in six people carry both copies of the allele.

"As a nation, we are eating more but doing less exercise, and so the average weight is increasing, but within the population some people seem to put on more weight than others," explains Professor Andrew Hattersley from the Peninsula Medical School. "Our findings suggest a possible answer to someone who might ask 'I eat the same and do as much exercise as my friend next door, so why am I fatter?' There is clearly a component to obesity that is genetic."

The researchers currently do not know why people with copies of the FTO allele have an increased BMI and rates of obesity.

"Even though we have yet to fully understand the role played by the FTO gene in obesity, our findings are a source of great excitement," says Professor Mark McCarthy from the University of Oxford. "By identifying this genetic link, it should be possible to improve our understanding of why some people are more obese, with all the associated implications such as increased risk of diabetes and heart disease. New scientific insights will hopefully pave the way for us to explore novel ways of treating this condition."
Major genetic study identifies gene for obesity

The findings were welcomed by Dr Mark Walport, Director of the Wellcome Trust.

"This is an exciting piece of work that illustrates why it was so important to sequence the human genome," says Dr Walport. "Obesity is one of the most challenging problems for public health in the UK. The discovery of a gene that influences the development of obesity in the general population provides a new tool for understanding how some people appear to gain weight more easily than others. This discovery, along with further results expected from the Wellcome Trust Case Control Consortium later this year, will open up a wealth of new avenues to understand and treat common diseases."

The FTO gene was first discovered whilst studying the DNA of a cohort of patients with type 2 diabetes. The risk of developing type 2 diabetes increases significantly for obese people. Through its effect on BMI, having one copy of the FTO allele increases the risk of developing type 2 diabetes by 25 per cent, having two by 50 per cent.

"We welcome this result, which holds promise for tackling rising levels of obesity and the associated risk of developing type 2 diabetes," says Professor Simon Howell, Chair of Diabetes UK, which funded the original collection of samples from people with diabetes. "The discovery has been possible not only because of exemplary team work of scientists from a large number of institutions but also because of the cooperation of the 5,000 diabetes patients and 37,000 people without diabetes who gave blood samples for the study."


Original research article: http://www.sciencemag.org/cgi/content/abstract/1141634v1 
DOI of the scientific paper: DOI: 10.1126/science.1141634 
Publication: Frayling T et a. A common variant in the FTO gene region is associated with body mass index in the general population and predisposes to adult and childhood obesity. Science 2007. 
On the web: www.pms.ac.uk/pms 

Funding information and declaration of competing interests: Funded by the Wellcome Trust, the UK's largest medical research charity. This study was part of the Wellcome Trust Case Control Consortium, which is searching for genetic variations that may predispose people to or protect them from major diseases.

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 About Dr. Sanjukta Acharya
This news story has been reviewed by Dr. Sanjukta Acharya before its publication on RxPG News website. Dr. Sanjukta Acharya, MBBS is the chief editor for RxPG News website. She oversees all the medical news submissions and manages the medicine section of the website. She has a special interest in diabetes and endocrinology.
RxPG News is committed to promotion and implementation of Evidence Based Medical Journalism in all channels of mass media including internet.
 Additional information about the news article
The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £500 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.

The Wellcome Trust Case Control Consortium (WTCCC) is a collaboration of 24 leading human geneticists at a number of institutes throughout the UK, who are analysing over 19 000 DNA samples from patients suffering with different diseases to identify common genetic variations for each condition. It is searching for the genetic signposts for tuberculosis, coronary heart disease, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, Crohn's disease, bipolar disorder and hypertension. As a second project the WTCCC is also analysing 15 000 polymorphic markers that alter protein sequence to look for genetic variations relating to another four diseases - breast cancer, autoimmune thyroid disease, multiple sclerosis and ankylosing spondylitis.

The Peninsula College of Medicine and Dentistry is the overarching entity for the Peninsula Medical School and the Peninsula Dental School. It is a joint entity of the Universities of Exeter and Plymouth. The first cohort of medial students joined in 2002. The first cohort of dental students will begin studies in September of this year. As well as teaching the doctors and dentists of tomorrow, the Peninsula College of Medicine and Dentistry undertakes a wide range of nationally and internationally recognised research in areas such as diabetes, cancer, heart disease, pulmonary disease, chronic fatigue syndrome/ME, MS, complementary therapies, genetics, vascular cell biology, childhood obesity and endocrinology.

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.

Diabetes UK is the charity for people with diabetes, their family friends and carers. Its mission is to improve the lives of people with the condition and work towards a future without diabetes by funding research, campaigning and helping people live with the condition. For more information, call Sarah Milsom in the press office on 020 7424 1164. People can call the Diabetes UK Careline on 0845 120 2960 for further support and information about diabetes.
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