Saliva provides a new trail in obesity genetics

April 8, 2014 by Laetitia Louis
Saliva provides a new trail in obesity genetics

Salivary amylase is a gene present in humans. Yet its number of copies can vary from one to 20, depending on the individual. Having a low copy number of the gene, which digests complex sugars (starches), favors obesity, according to an international team led by Professor Philippe Froguel from the Genomique et Maladies Métaboliques laboratory (CNRS/Université Lille 2/Institut Pasteur de Lille). The researchers showed that people with the smallest number of salivary amylase copies (and therefore low amylase levels in the blood) are ten times more at risk of becoming obese. With each unit drop in the number of copies of this gene, the risk of obesity increases by 20%. This work, published on March 30, 2014 in Nature Genetics, reveals for the first time a genetic link between complex carbohydrate digestion and obesity.

One billion people worldwide are overweight. Although obesity has an environmental origin at the population level, in individuals, 70% of the genetic risk in subjects predisposed to obesity is due to genetic factors. About 5% of morbidly obese people carry a mutation in one of the genes that controls appetite, which is enough to make them obese. Recent pan-genomic studies using DNA microarrays identified 70 common obesity genes, but their impact is low and only explains a small part of the genetic risk (4%).

French and British researchers went further by studying obesity-discordant Swedish siblings, analyzing their genome and the genes in adipose tissue, which are expressed differently in obese subjects and in those with normal weight. They identified a region in chromosome 1 that is unique because it contains a gene, (AMY1), present in a single form in humans. Instead of having only two copies of this gene (one from the father, one from the mother) the number of AMY1 copies varies in humans from one to 20. For 10,000 years, since agriculture began, the number of AMY1 copies has increased, evidence of natural selection and human evolution: since amylase digests complex sugars (), individuals who secrete high levels of salivary amylase have a selective nutritional advantage. Researchers have noticed that people with the smallest number of AMY1 copies (and therefore little amylase enzyme in their blood) are ten times more at risk of becoming obese. With each unit drop in the number of AMY1 copies, the risk of obesity increases by 20%. Alone, this region of the genome explains almost 10% of the genetic risk.

There are two forms of amylase: one produced by the pancreas and the other by the salivary glands. Only the salivary form seems to be associated with obesity. It is not yet known why a salivary amylase deficiency increases obesity: two hypotheses are under consideration. The first is that chewing and partially digesting food in the mouth could have a hormonal effect inducing satiety, which would be reduced in the case of AMY1 deficiency. The second is that poor starch digestion could change the intestinal flora, thereby contributing indirectly to obesity or even diabetes. That is what initial metabolomic studies conducted in patients with high or low salivary amylase suggest. Thus, individuals with low salivary amylase have abnormally high glycemia when they eat starch.

These entirely novel findings point to a genetic predisposition to obesity via complex carbohydrate digestion and its effects on the intestinal bacterial flora. They open important perspectives for more effective prevention and treatment that take into account food digestion and degradation in the intestines.

Explore further: New study finds strong link between obesity and 'carb breakdown' gene

More information: "Low copy number of the salivary amylase gene predisposes to obesity." Mario Falchi, et al. Nature Genetics, March 30, 2014. DOI: 10.1038/ng.2939

Related Stories

New study finds strong link between obesity and 'carb breakdown' gene

March 30, 2014
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, published in Nature ...

Enzyme in saliva helps regulate blood glucose

April 4, 2012
Scientists from the Monell Center report that blood glucose levels following starch ingestion are influenced by genetically-determined differences in salivary amylase, an enzyme that breaks down dietary starches. Specifically, ...

Stress can delay pregnancy and double the risk of infertility, study finds

March 24, 2014
Having difficulty getting pregnant can be an incredibly stressful experience for any couple. Now, for the first time, researchers have data that suggests preconception stress might play a role in infertility.

Parental obesity and autism risk in the child

April 7, 2014
Several studies have looked at possible links between maternal obesity during pregnancy and the risk of developmental disorders in the child. However, paternal obesity could be a greater risk factor than maternal obesity, ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.