Friday, April 13, 2007

'Fat' gene found by scientists

A gene that contributes to obesity has been identified for the first time, promising to explain why some people easily put on weight while others with similar lifestyles stay slim.

People who inherit one version of the gene rather than another are 70 per cent more likely to be obese, British scientists have discovered. One in six people has the most vulnerable genetic make-up and weighs an average 3kg more than those with the lowest risk. They also have 15 per cent more body fat.

The findings provide the first robust link between a common gene and obesity, and could eventually lead to new ways of tackling one of the most significant causes of ill health in the developed world. One in four British adults is classified as obese, and half of men and a third of women are overweight.

Obesity is a main cause of heart disease, cancer and type 2 diabetes. An adviser to the Government’s health spending watchdog said recently that the condition was a bigger national danger than smoking, alcohol or poverty.

If the biological function of the gene, known as FTO, can now be understood, it could become possible to design drugs that manipulate it to help people to control their weight. “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,” Mark McCarthy, of the University of Oxford, who led the research, said.

“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 insights will hopefully pave the way for us to explore novel ways of treating this condition.”

While it has long been understood from family studies that obesity is heavily influenced by genetics, scientists have struggled to pin down individual genes that are involved.

A handful of serious genetic mutations that cause rare obesity disorders such as Prader-Willi Syndrome have been found, but the search for common genes that affect an ordinary person’s risk of becoming obese or overweight has remained elusive.

The effect of FTO emerged from a key study of the genetic origins of disease funded by the Wellcome Trust known as the Case Control Consortium, in which 2,000 people with type 2 diabetes had their genomes compared to 3,000 healthy controls.

Scientists from Oxford and the University of Exeter first found that certain versions of the FTO gene were more common among people with type 2 diabetes, but that the effect disappeared when the data were adjusted for obesity. This led them to wonder whether FTO really influenced obesity instead, and they followed up their theory in a further 37,000 people.

FTO comes in two varieties, and everyone inherits two copies of the gene. The team found that those who inherit two copies of one variant — 16 per cent of white Europeans — were 70 per cent more likely to be obese than those who inherited two copies of the other variant. The 50 per cent of subjects who inherited one copy of each FTO variant had a 30 per cent higher risk of obesity.

Those in the highest risk group weighed an average of 3kg (7lb) more and those at medium risk were an average of 1.2kg heavier. In each case the extra weight was entirely accounted for by more body fat, not greater muscle or extra height. The results, published in the journal Science, apply to men and women, and to children as young as 7.

FTO will not be the only gene that influences obesity, and inheriting a particular variant will not necessarily make anyone fat. “This is not a gene for obesity, it is a gene that contributes to risk,” Professor McCarthy said.

The research involved too many people to control for exercise and diet, so it is not yet known whether FTO affects how much people eat or how active they are. But it may explain how people with apparently similar lifestyles differ in propensity to put on weight.

Independent experts called the discovery highly significant. Susan Jebb, of the MRC Human Nutrition Unit, said: “This research provides clear evidence of a biological mechanism which makes some people more susceptible to gaining weight in a world where food is plentiful and sedentary lifestyles the norm.”

Genetic trigger

— The FTO gene comes in two varieties. 16% of people have two copies of the high-risk variant, 50% have one high-risk and one low-risk, and 34% of people have two low-risk variants

— Those with two high-risk copies have a 70% greater risk of obesity than those with two low-risk copies. They weigh an average of 3kg more

— Those with one high-risk copy have a 30% greater risk of obesity. They weigh an average of 1.2kg more



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