Obesity linked to genetic variation in carbohydrate digestion

Obesity might not simply be a matter of overeating or heightened appetite but is at least partially down to how we metabolise food, a study says.

Whereas previous research has concentrated on genes that influence appetite or eating behaviour to increase our likelihood of being overweight, new research has found that a gene involved in carbohydrate digestion may exert a strong influence. The findings suggest that two people of similar height and build could eat identical diets but only one would become overweight.

Dr Julia El-Sayed Moustafa, a co-lead author from Imperial College London, said: 'This paper is novel in that it identifies a genetic variation that is both common and has a relatively large effect on the risk of obesity in the general population'.

The researchers were interested in the effect of a phenomenon called copy number variation on body mass index (BMI). Copy number variation describes the fact that although people usually have two copies of each gene, this can vary in some sections of our DNA.

They started by looking at genetic data from a Swedish twin study involving 481 participants and soon found that copy number variation in AMY1, a gene coding for a digestive enzyme called salivary amylase seemed to exert a particularly strong effect on BMI. The more copies of AMY1 people had, the less likely they were to be obese.

The finding was repeated in two other datasets comprising genetic information from just under 6,000 people.

The number of copies of AMY1 is highly variable across the population. The researchers estimate that there is roughly a 20 percent decrease in the chance of becoming obese carried with every additional AMY1 gene.

Salivary amylase is the first enzyme encountered by food when it enters the mouth, beginning a digestive process that continues in the gut. People with fewer copies of the gene may have lower levels of the enzyme and so not break down carbohydrates as well as those with more copies.

However, first author Dr Mario Falchi told New Scientist that this explanation does not take into account amylase produced in the pancreas. He suggests that AMY1 copy number variation may exert its influence 'through more complex mechanisms such as influencing signalling pathways, or changing the gut microbiota'.

Joint lead investigator Professor Tim Spector of King's College London said that the knowledge that individual differences in metabolism can influence weight gain may have considerable impact on the public health approach to obesity.

'In the future, a simple blood or saliva test might be used to measure levels of key enzymes such as amylase in the body and therefore shape dietary advice for both overweight and underweight people', he said, before adding that 'treatments are a long way away'.

The research was published in Nature Genetics.