Copy number variation of human AMY1 is a minor contributor to variation in salivary amylase expression and activity

Danielle Carpenter,Laura M Mitchell,John A L Armour

doi:10.1186/s40246-017-0097-3

Danielle Carpenter, Laura M Mitchell + Show 1 more

Open Access

https://doi.org/10.1186/s40246-017-0097-3

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Journal: Human genomics	Publication Date: Feb 20, 2017
Citations: 37	License type: open-access

Affiliation: University of Nottingham

Abstract

BackgroundSalivary amylase in humans is encoded by the copy variable gene AMY1 in the amylase gene cluster on chromosome 1. Although the role of salivary amylase is well established, the consequences of the copy number variation (CNV) at AMY1 on salivary amylase protein production are less well understood. The amylase gene cluster is highly structured with a fundamental difference between odd and even AMY1 copy number haplotypes. In this study, we aimed to explore, in samples from 119 unrelated individuals, not only the effects of AMY1 CNV on salivary amylase protein expression and amylase enzyme activity but also whether there is any evidence for underlying difference between the common haplotypes containing odd numbers of AMY1 and even copy number haplotypes.ResultsAMY1 copy number was significantly correlated with the variation observed in salivary amylase production (11.7% of variance, P < 0.0005) and enzyme activity (13.6% of variance, P < 0.0005) but did not explain the majority of observed variation between individuals. AMY1-odd and AMY1-even haplotypes showed a different relationship between copy number and expression levels, but the difference was not statistically significant (P = 0.052).ConclusionsProduction of salivary amylase is correlated with AMY1 CNV, but the majority of interindividual variation comes from other sources. Long-range haplotype structure may affect expression, but this was not significant in our data.

Highlights

The enzyme amylase plays a major role in starch hydrolysis, which begins in the oral cavity and continues into the stomach and small intestine
Whilst it has been suggested that quantitative variation in amylase protein patterns does not always reflect variation in the amylase gene cluster [5], some studies have shown a relationship between the observed copy number variation (CNV) at the salivary amylase gene
Variation in AMY2 copy number was observed with AMY2A copy variable in 24% of samples and AMY2B showing CNV in about 10% of samples (Table 1)

Summary

Introduction

The enzyme amylase plays a major role in starch hydrolysis, which begins in the oral cavity and continues into the stomach and small intestine. Amylase is the most abundant protein in saliva, accounting for at least 50% of salivary protein [1], but the quantity and enzyme activity of salivary amylase varies greatly among individuals This variation in amylase production could be attributable to a number of factors including environmental factors, such as stress [2] and circadian rhythms [3], oral health [4] and the genetic background of an individual’s amylase gene cluster. Mandel and colleagues [6], using immunoblotting, observed a similar correlation (R = 0.50) with copy number at AMY1 and amylase protein levels as well as a correlation (R = 0.52) between CNV at AMY1 and salivary enzyme activity These results suggest that approximately 20–35% of the variance in salivary amylase expression can be attributed to variation in AMY1 copy number. We aimed to explore, in samples from 119 unrelated individuals, the effects of AMY1 CNV on salivary amylase protein expression and amylase enzyme activity and whether there is any evidence for underlying difference between the common haplotypes containing odd numbers of AMY1 and even copy number haplotypes

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