by John Toscano

Created on: April 15, 2008

It has long been suspected that there is a genetic predisposition to obesity but finding a gene or genes responsible has proved elusive. When a clear suspect did emerge, it turned out to be a gene that was already well known, but for different reasons. In 1989 it was found that deletions in a section of DNA in mice resulted in a gene variant that was found to cause fused toes (FT) and other (O) abnormalities, the gene involved, and its variant, came to be known as the FTO gene. Later, in 1999, when someone coined the nickname of "Fatso" for the gene, they could scarcely have guessed that eight years later the same gene would hit the headlines as providing a genetic link with obesity. Prior to this, there was already strong evidence to suggest that the tendency to become obese is heavily determined by genetic factors. Critical evidence for this came from a study that compared data obtained from identical and non-identical twins. This study was based on the reasonable assumption that two children who are twins are likely to be raised in the same environment and eat a similar diet. The researchers showed that the tendency towards obesity varied much more between non-identical twins than between identical twins and calculated from the data that, of the factors determining obesity, more than three-quarters were genetic.

The next task was to identify a gene or genes that might be responsible for these observations. The FTO gene, which is located on chromosome 16 in humans, had already come under scrutiny after a series of investigations had implicated it as being linked to type 2 diabetes. This disease develops because individuals become resistant to insulin, the hormone that facilitates the uptake of glucose by cells, a critical element in the control of blood glucose levels. In obese people, the cells often lose their sensitivity to glucose, causing a rise in blood glucose levels as glucose remains in the blood. Fat cells appear to be more resistant to insulin than muscle cells, so that the more obese as person is, the greater will be their insensitivity to insulin and the more likely it is that type 2 diabetes will develop.

This year saw the publication of work by the Peninsula Medical School and Oxford University, whose data revealed for the first time the extent to which the FTO gene variant affects obesity. The extent of the effect depends on whether a person has one or two copies of the variant. Persons born with one copy of the gene variant carry an estimated

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