Starch intake, amylase gene copy number variation, plasma proteins, and risk of cardiovascular disease and mortality

Abstract

Background Salivary amylase, encoded by the AMY1 gene, initiate the digestion of starch. Whether starch intake or AMY1 copy number is related to disease risk is currently rather unknown. The aim was to investigate the association between starch intake and AMY1 copy number and risk of cardiovascular disease (CVD) and mortality and whether there is an interaction. In addition, we aim to identify CVD-related plasma proteins associated with starch intake and AMY1 copy number. Methods This prospective cohort study used data from 21,268 participants from the Malmö Diet and Cancer Study. Dietary data were collected through a modified diet history method and incident CVD and mortality were ascertained through registers. AMY1 gene copy number was determined by droplet digital polymerase chain reaction, a risk score of 10 genetic variants in AMY1 was measured, and a total of 88 selected CVD-related proteins were measured. Cox proportional hazards regression was used to analyze the associations of starch intake and AMY1 copy number with disease risk. Linear regression was used to identify plasma proteins associated with starch intake and AMY1 copy number. Results Over a median of 23 years’ follow-up, 4443 individuals developed CVD event and 8125 died. After adjusting for potential confounders, a U-shape association between starch intake and risk of CVD (P-nonlinearity = 0.001) and all-cause mortality (P-nonlinearity = 0.03) was observed. No significant association was found between AMY1 copy number and risk of CVD and mortality, and there were no interactions between starch intake and AMY1 copy number (P interaction > 0.23). Among the 88 plasma proteins, adrenomedullin, interleukin-1 receptor antagonist protein, fatty acid-binding protein, leptin, and C-C motif chemokine 20 were associated with starch intake after adjusting for multiple testing. Conclusions In this large prospective study among Swedish adults, a U-shaped association between starch intake and risk of CVD and all-cause mortality was found. Several plasma proteins were identified which might provide information on potential pathways for such association. AMY1 copy number was not associated with CVD risk or any of the plasma proteins, and there was no interaction between starch intake and AMY1 copy number on disease risk.