Researchers at King's College London and Imperial College London
have discovered that people with fewer copies of a gene coding for
a carb-digesting enzyme may be at higher risk of obesity.
The findings suggest that dietary advice may need to be more
tailored to an individual's digestive system, based on whether they
have the genetic predisposition and necessary enzymes to digest
different foods.
Salivary amylase plays a significant role in breaking down
carbohydrates in the mouth at the start of the digestion process.
The new study suggests that people with fewer copies of the AMY1
gene have lower levels of this enzyme and therefore will have more
difficulty breaking down carbohydrates than those with more
copies.
Previous research has found a genetic link between obesity and
food behaviours and appetite, but the new discovery highlights a
novel genetic link between metabolism and obesity. It suggests that
people's bodies may react differently to the same type and amount
of food, leading to weight gain in some and not in others. The
effect of the genetic difference found in the latest study appears
much stronger link than any of those found before.
Researchers first measured gene expression patterns in 149
Swedish families with differences in the levels of obesity and
found unusual patterns around two amylase genes (AMY1 and AMY2),
which code for salivary and pancreatic amylase. This was suggestive
of a variation in copy numbers relating directly to obesity.
The finding was replicated strongly in 972 twins from TwinsUK,
the biggest UK adult twin registry, which found a similar pattern
of expression. The researchers then estimated the precise copy
numbers of the amylase gene in the DNA of a further 481 Swedish
subjects, 1,479 subjects from TwinsUK and 2,137 subjects from the
DESIR project.
The collaborative team found that the number of copies of the
AMY1 gene (salivary amylase) was consistently linked to obesity.
Further replication in French and Chinese patients with and without
obesity showed the same patterns.
A lower estimated AMY1 copy-number showed a significantly
increased risk of obesity in all samples and this translated to an
approximate eight-fold difference in the risk of obesity between
those subjects with the highest number of copies of the gene and
those with the lowest.
Standard genome-wide mapping methods had missed this strong
association as the area is technically hard to map. This variation
in copy numbers, also known as 'copy number variants' (CNV) has
been underestimated as a genetic cause of disease, but the link
between CNV in the amylase gene and obesity provides an indication
that other major diseases may be influenced by similar
mechanisms.
Professor Tim Spector, Head of the Department of Twin Research
and Genetic Epidemiology at King's said: "'These findings are very
exciting. While studies to date have mainly found small effect
genes that alter eating behaviour, we discovered how the digestive
'tools' in your metabolism - and the genes coding for these - vary
between people and can have a large influence on your weight.
"The next step is to find out more about the activity of this
digestive enzyme, and whether it might prove a useful biomarker or
target for the treatment of 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. Treatments are a long way away but this is an important
step in realising that all of us digest and metabolise food
differently - and we can move away from 'one-size fits all' diets
to more personalised approaches."
The paper, Low copy number of the salivary amylase gene predisposes to
obesity, is published in Nature Genetics.