Clinical and Evolutionary Consequences of Human Amylase Variation
Research type
Research Study
Full title
Clinical and Evolutionary Consequences of Human Amylase Variation
IRAS ID
190715
Contact name
John Armour
Contact email
Sponsor organisation
University of Nottingham
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
In this pilot project we will test whether newly discovered variation in the copy number of pancreatic amylase genes is a predisposing factor in pancreatic cancer or pancreatitis. For both these debilitating disorders there are few clues to the underlying pathology, or biomarkers allowing early diagnosis. Definition of at-risk subgroups of the population would allow appropriate screening, and early detection for pancreatic cancer in particular would greatly enhance the prospects for increased survival.
Among the many digestive enzymes secreted by the pancreas, pancreatic amylase is a key enzyme for the breakdown of dietary starch. When we first chew a mouthful of bread, for example, digestion of the starch begins with an amylase enzyme found in saliva. However, the action of that salivary enzyme is brief (it is stopped by acid in the stomach after swallowing) and does not complete the starch digestion, which needs to be finished off in the duodenum by the action of pancreatic amylase. For many years it has been appreciated that people vary in the numbers of genes for salivary amylase, and there is good evidence that this variation is also reflected in varying amounts of amylase in saliva. By contrast, there has been little characterisation until very recently of variation in pancreatic amylase genes, and we have discovered that the pancreatic amylase genes can also vary in copy number between individuals. Worldwide, most people have four pancreatic amylase genes, two copies each of the subtly different AMY2A and AMY2B genes. However, our work shows that people often have other numbers of these genes; in Europe, for example, there is a common deletion of the AMY2A gene, so that about 15% of the population have 3 pancreatic amylase genes instead of 4. There is also a duplication affecting both AMY2A and AMY2B, so that about 12% of Europeans have a total of 6 copies.
We would predict that these gene variants should be reflected in the efficiency of starch digestion in the small bowel, and in particular that uncommon individuals (about 1 in 200) with two copies of the AMY2A deletion would have considerably less pancreatic amylase than most people. We will be investigating the possible correlation of this variation with a wider range of digestive symptoms in parallel studies, but in this work we will test the simple question of association – is variation in pancreatic amylase gene number associated with acute and chronic pancreatitis, or with pancreatic cancer? Recent work has discovered that variants in the genes for the protein-digesting enzymes trypsin and chymotrypsin are associated with inherited predisposition to pancreatitis, in both chronic and recurrent acute presentations, and we will test the hypothesis that variation in amylase may be similarly associated with pancreatic pathology.
REC name
South Central - Berkshire Research Ethics Committee
REC reference
15/SC/0707
Date of REC Opinion
16 Nov 2015
REC opinion
Favourable Opinion