The physiological significance of AMY1 gene copy number variation

Abstract

The AMY1 gene codes for salivary α-amylase (sAA), the enzyme responsible for commencing starch digestion. Humans show unusually high copy number variation (CNV) in AMY1. This thesis examined the potential phenotypic consequences of AMY1 CNV on sAA activity, starch digestion, food intake, and the metabolic responses to starchy foods. Fasting blood and saliva samples, along with anthropometric and dietary intake data, were collected from 201 predominantly young, lean, healthy individuals. AMY1 copy number ranged from 1 – 16 copies, with an average of 6.5 ± 2.6 copies. Individuals with Asian ethnicity had significantly higher average AMY1 copy number (7.7 ± 0.4 copies) compared to Caucasians (6.1 ± 0.2 copies) (p < 0.0001). AMY1 CNV explained ~40% of the variation in sAA activity (r = 0.62, p < 0.0001). Individuals with higher AMY1 copy number reported consuming less total energy (highest quintile vs lowest quintile: ~1000 kJ less, p = 0.027) but more starch as a proportion of energy intake (p = 0.041 for trend). Relative glycaemic responses (expressed as glycaemic index, GI) to white bread and pasta were ~15% greater in the high AMY1 copy number group (n = 20, 10.4 ± 1.6 copies) compared to those with lower copy number (n = 20, 3.1 ± 0.9 copies) (p < 0.05 for both foods). Acute satiety responses to white bread were ~50% higher in the high vs low AMY1 group (p = 0.023). AMY1 copy number was a significant predictor of the GI of a range of starchy foods, explaining 26 - 61% of the variation in GI (p < 0.001 for all foods). Taken together, AMY1 CNV strongly influences sAA activity resulting in significant differences in acute postprandial glucose and insulin responses to starchy foods. AMY1 copy number may influence energy balance via acute and chronic satiety mechanisms. The ability of AMY1 genotyping to predict starch digestibility and postprandial responses has the potential to identify individuals at greater risk of developing impairments in glucose metabolism.