Dietary starch intake modifies the relation between copy number variation in the salivary amylase gene and BMI

Abstract

Background: Studies have shown conflicting associations between the salivary amylase gene (AMY1) copy number and obesity. Salivary amylase initiates starch digestion in the oral cavity; starch is a major source of energy in the diet. Objective: We investigated the association between AMY1 copy number and obesity traits, and the effect of the interaction between AMY1 copy number and starch intake on these obesity traits. Design: We first assessed the association between AMY1 copy number (genotyped by digital droplet polymerase chain reaction) and obesity traits in 4800 individuals without diabetes (mean age: 57 y; 60% female) from the Malmö Diet and Cancer Cohort. Then we analyzed interactions between AMY1 copy number and energyadjusted starch intake (obtained by a modified diet history method) on body mass index (BMI) and body fat percentage. Results: AMY1 copy number was not associated with BMI (P = 0.80) or body fat percentage (P = 0.38). We observed a significant effect of the interaction between AMY1 copy number and starch intake on BMI (P-interaction = 0.007) and body fat percentage (P-interaction = 0.03). Upon stratification by dietary starch intake, BMI tended to decrease with increasing AMY1 copy numbers in the low-starch intake group (P = 0.07) and tended to increase with increasing AMY1 copy numbers in the high-starch intake group (P = 0.08). The lowest mean BMI was observed in the group of participants with a low AMY1 copy number and a high dietary intake of starch. Conclusions: Our findings suggest an effect of the interaction between starch intake and AMY1 copy number on obesity. Individuals with high starch intake but low genetic capacity to digest starch had the lowest BMI, potentially because larger amounts of undigested starch are transported through the gastrointestinal tract, contributing to fewer calories extracted from ingested starch.Am J Clin Nutr 2017;106:256-62.

No Evidence for Association of BMI with Salivary Amylase Gene Copy Number in the UK 1958 Birth Cohort

“…A study of the AMY1 copy number in 4,800 nondiabetic adult participants did not replicate the simple association found by Falchi et al between the AMY1 copy number and BMI ( P = 0.8) but provided evidence of dependence of the relationship between the AMY1 copy number and BMI on dietary starch intake. Plasma enzyme activity was significantly associated both with the AMY1 gene copy number and with BMI in the well‐characterized DESIR cohort, but the association between BMI and the AMY1 copy number was only nominally significant ( P = 0.023) .…”

“…Our study has the obvious limitation that BMI is the only phenotype analyzed, with sex and, in some analyses, age as covariates; we have no information on potentially relevant environmental or lifestyle factors such as nutrition. An association conditional on lifestyle factors not recorded in our study, such as dietary starch intake , could therefore escape detection if the association could not be detected without allowance for this covariate. Indeed, the study of 4,800 nondiabetic participants with a mean age of 57 years by Rukh et al demonstrated no significant association of BMI with AMY1 copy number alone ( P = 0.8) but found a significant interaction ( P = 0.007) conditional upon dietary starch intake.…”

“…An association conditional on lifestyle factors not recorded in our study, such as dietary starch intake (7), could therefore escape detection if the association could not be detected without allowance for this covariate. Indeed, the study of 4,800 nondiabetic participants with a mean age of 57 years by Rukh et al (7) demonstrated no significant association of BMI with AMY1 copy number alone (P = 0.8) but found a significant interaction (P = 0.007) conditional upon dietary starch intake. That study used droplet digital PCR to determine the AMY1 copy number, and the excess of samples with even numbers of copies reassures that the accuracy of copy number determination is likely to be high.…”

“…The main association analyses described in this study used the subset of the UK 1958 Birth Cohort included as control subjects in the WTCCC CNV analysis (3). The UK 1958 Birth Cohort study initially sampled 17,416 children born in the UK in the same week in 1958, and data sweeps, including interviews and biometric measurements, were conducted at ages 7,11,16,23,33,42,44, and 50 years (13). Loss to follow-up meant that by age 50, there were data from 9,790 participants.…”

On the origin of obesity: identifying the biological, environmental and cultural drivers of genetic risk among human populations

“…This relationship, however, was recently shown to be modified by starch intake. Rukh and colleagues observed decreased BMI with increasing copies of AMY1 and low starch intake but elevated BMI with increasing copies of AMY1 among those with high starch intake. Perry and colleagues show that populations that consume more starch rich diets have more AMY1 copies, while copy number variation among populations consuming lower amounts of starch results from genetic drift.…”