AMY1 Gene Copy Number Correlates With Glucose Absorption and Visceral Fat Volume, but Not with Insulin Resistance.

BACKGROUND: The human amylase gene (AMY1) has a broad copy number (CN) variation that may associate with body mass index. METHODS: Deoxyribonucleic acid was extracted from urine (n = 74) and serum (n = 6) samples (Protein, Fiber and Metabolic Syndrome [ProFiMet] cohort), and buccal (n = 17) samples (Oral Starch Challenge [OSC] cohort), and assessed for AMY1 CN by droplet digital polymerase chain reaction. The association of AMY1 CN with comprehensive markers of metabolic status (ProFiMet cohort) were analyzed with Pearson's correlation coefficient (CC). For the healthy, euglycemic OSC cohort, glycemic response to OSC was analyzed with independent sample t-tests (subgroups: high AMY1 CN 9-12, n = 10; low AMY1 CN 4-6, n = 7). RESULTS: There were significant inverse correlations of AMY1 CN with total visceral fat volume (CC -0.33; P = 0.004) and positive correlations of AMY1 CN with oral glucose insulin sensitivity score (derived from an oral glucose tolerance test, CC 0.26; P = 0.02), serum HDL-cholesterol (CC 0.325; P = 0.003), and serum adiponectin (CC 0.249; P = 0.026). Linear regression multivariate analysis (adiponectin as dependent variable), showed independent association of adiponectin with AMY1 CN (Beta = 0.29; P = 0.03). There were no significant associations between AMY1 CN and clamp-derived M-value, homeostasis model assessment of insulin resistance (IR), hepatic endogenous glucose production, fecal floral signature, or macronutrient dietary preference. Delta (mean) change in blood glucose concentration (fasting to 30-minutes post-OSC) was significantly greater in the high versus low AMY1 CN subgroups (mean 1.7 mmol/l [SEM 0.6] vs 0.9 mmol/l [SEM 0.9], respectively; P = 0.016). CONCLUSIONS: High AMY1 CN associates with a favorable metabolic profile (lower visceral fat volume, higher serum adiponectin, enhanced glucose absorption following oral glucose, and OSC), but not with whole-body or hepatic IR.

Human amylase gene copy number variation as a determinant of metabolic state.

INTRODUCTION: Humans have multiple genes encoding amylase that are broadly divided into salivary (AMY1) and pancreatic (AMY2) genes. They exhibit some of the greatest copy numbers of any human gene, an expansion possibly driven by increased dietary starch intake. Within the population, amylase gene copy number is highly variable and there is evidence of an inverse association between AMY1 copy number and BMI. AREAS COVERED: We examine the evidence for the link between AMY1 and BMI, its potential mechanisms, and the metabolic effects of salivary and pancreatic amylase, both in the gastrointestinal tract and the blood EXPERT COMMENTARY: Salivary amylase may influence postprandial 'cephalic phase' insulin release, which improves glucose tolerance, while serum amylase may have insulin-sensitizing properties. This could explain the favorable metabolic status associated with higher AMY1 copy number. The association with BMI is harder to explain and is potentially mediated by increased flux of undigested starch into the ileum, with resultant effects on short-chain fatty acids (SCFAs), changes in gut microbiota and effects on appetite and energy expenditure in those with low copy number. Future research on the role of amylase as a determinant of metabolic health and BMI may lead to novel therapies to target obesity.