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

Abstract

Background: Salivary 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.

Results: AMY1 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).

Conclusions: Production 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.

Keywords: Amylase; CNV; Gene expression; Genome instability.

Fig. 1

Distribution histogram of AMY1 copy number in 119 unrelated UK samples; a clear majority have even copy numbers (89 out of 119)

Fig. 2

A box and whiskers plot of amylase protein concentration by AMY1 copy number, with mean for all samples at a given copy number shown as a black bar, the standard deviation as the box, and whiskers showing the observed full range of data. Each contributing data point is the mean of three experimental replicates, and further details of biological replicates from the same subjects can be found in the “Methods”

Fig. 3

A box and whiskers plot of amylase enzyme activity by AMY1 copy number, with mean of all samples at each copy number shown as a black bar, and whiskers showing the observed range of data. The boxes indicate the standard deviation at each copy number. Each data point used in the analysis is the mean of two experimental replicates, and further details of biological replicates from the same subjects can be found in the “Methods”