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Background  Copy number (CN) variation (CNV) of the salivary amylase gene ( AMY1 ) influences the ability to digest starch and may influence glucose homeostasis, obesity and gut microbiota composition. Hence, the aim was to examine the association of  AMY1  CNV with fasting glucose, BMI, and gut microbiota composition considering habitual starch intake and to investigate the effect of  AMY1  CNV on the postprandial response after two different starch doses.    Methods  The Malmö Offspring Study ( n  = 1764, 18–71 years) was used to assess interaction effects between  AMY1  CNV (genotyped by digital droplet polymerase chain reaction) and starch intake (assessed by 4-day food records) on fasting glucose, BMI, and 64 gut bacteria (16S rRNA sequencing). Participants with low (≤ 4 copies,  n  = 9) and high (≥ 10 copies,  n  = 10)  AMY1  CN were recruited for a crossover meal study to compare postprandial glycemic and insulinemic responses to 40 g and 80 g starch from white wheat bread.    Results  In the observational study, no overall associations were found between  AMY1  CNV and fasting glucose, BMI, or gut microbiota composition. However, interaction effects between  AMY1  CNV and habitual starch intake on fasting glucose ( P  = 0.03) and BMI ( P  = 0.05) were observed, suggesting inverse associations between  AMY1  CNV and fasting glucose and BMI at high starch intake levels and positive association at low starch intake levels. No associations with the gut microbiota were observed. In the meal study, increased postprandial glucose ( P  = 0.02) and insulin ( P  = 0.05) were observed in those with high  AMY1  CN after consuming 40 g starch. This difference was smaller and nonsignificant after consuming 80 g starch.    Conclusions  Starch intake modified the observed association between  AMY1  CNV and fasting glucose and BMI. Furthermore, depending on the starch dose, a higher postprandial glucose and insulin response was observed in individuals with high  AMY1  CN than in those with low  AMY1  CN.    Trial registration   ClinicalTrials.gov ,  NCT03974126 . Registered 4 June 2019—retrospectively registered.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12263-021-00701-8.

genes and nutrition

Effect of AMY1 copy number variation and various doses of starch intake on glucose homeostasis: data from a cross-sectional observational study and a crossover meal study