Starch Digestion-Related Amylase Genetic Variants, Diet, and Changes in Adiposity: Analyses in Prospective Cohort Studies and a Randomized Dietary Intervention

Abstract

Salivary amylase, encoded by the AMY1 gene, is responsible for the digestion of carbohydrates. We investigated associations of AMY1 genetic variations with general and central adiposity changes considering dietary carbohydrate intake among 32,054 adults from four prospective cohort studies. A genetic risk score (GRS) was calculated based on nine AMY1 single-nucleotide polymorphisms, with higher AMY1-GRS indicating higher activity of salivary amylase. We meta-analyzed interactions between AMY1-GRS and dietary intake for changes in general and central adiposity over 5.5-10 years. We found that carbohydrate food intake significantly altered associations of AMY1-GRS with changes in BMI (P interaction = 0.001) and waist circumference (P interaction < 0.001). Results were consistent and significant in female cohorts rather than in male cohorts. Among women, higher AMY1-GRS was associated with more increases in adiposity if dietary carbohydrate food intake was high, while higher AMY1-GRS was associated with less gains in adiposity when the dietary intake was low. Also, in a 2-year randomized dietary intervention trial, associations of AMY1-GRS with changes in weight (P interaction = 0.023) and waist circumference (P interaction = 0.037) were significantly modified by carbohydrate intake. Our results suggest the importance of precision nutrition strategies considering participants' genetic adaptation to carbohydrate-rich diets in regulating general and central adiposity.

Trial registration: ClinicalTrials.gov NCT00072995.

© 2020 by the American Diabetes Association.

Figures

Figure 1

A: Sex differences in interaction effects of AMY1-GRS and dietary carbohydrate food intake for BMI changes with the test of effect size (ES): Pinteraction < 0.001 (women); Pinteraction = 0.44 (men); Pinteraction < 0.001 (overall). B: Sex differences in interaction effects of AMY1-GRS and dietary carbohydrate food intake for WC changes with the test of ES: Pinteraction < 0.001 (women); Pinteraction = 0.12 (men); Pinteraction < 0.001 (overall). The ES (95% CI) indicates the effect of interactions between AMY1-GRS (per 1 unit) and carbohydrate foods (per 1 SD) for changes in BMI or changes in WC after adjusting for the same covariates listed in Table 1 (except for sex).

Figure 2

Changes in BMI and changes in WC per 5-point increment in AMY1-GRS according to tertile categories of carbohydrate food intake in female and male cohorts. Data after adjusting for the same covariates listed in Table 1 (except for sex). A: Effect of AMY1-GRS across tertile 1 (T1) to tertile 3 (T3) of carbohydrate food intake in each cohort (NHS, ARIC-women, and UK Biobank-women) for changes in BMI. B: Effect of AMY1-GRS across T1 to T3 of carbohydrate food intake in each cohort (HPFS, ARIC-men, and UK Biobank-men) for changes in BMI. C: Effect of AMY1-GRS across T1 to T3 of carbohydrate food intake in each cohort (NHS, ARIC-women, and UK Biobank-women) for changes in WC. D: Effect of AMY1-GRS across T1 to T3 of carbohydrate food intake in each cohort (HPFS, ARIC-men, and UK Biobank-men) for changes in WC.

Figure 3

A: Effect of a per 5-unit increase in AMY1-GRS for changes in weight. B: Effect of a per 5-unit increase in AMY1-GRS for changes in WC. The effect is in response to low-calorie weight-loss diets varying in carbohydrate intake (35%, 45–55%, and 65% of total energy intake) in the POUNDS Lost trial. Bars indicate β and SE values for changes in weight or WC from 6 months to 2 years after dietary intervention per 5-unit increase in AMY1-GRS after adjustment for age, sex (in total participants), ethnicity, the initial value (at 6 months) of weight or WC. The number of total participants was 506, including 301 women and 205 men.