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

• Published in: The journal of clinical endocrinology and metabolism 2020-10, Vol.105 (10), p.e3586-e3596
• Main Authors: Barber, Thomas M, Bhatti, Ahsan A, Elder, Patrick J D, Ball, Sarah P, Calvez, Ronan, Ramsden, David B, Cuthbertson, Dan J, Pfeiffer, Andreas F, Burnett, David, Weickert, Martin O
• Format: Article
• Language: English
• Subjects: Adiponectin; Adipose tissues; Adiposity - genetics; Administration, Oral; AMY1 gene; Amylases; Blood glucose; Blood Glucose - analysis; Blood Glucose - genetics; Blood Glucose - metabolism; Blood levels; Body composition; Body Mass Index; Cholesterol; Cohort Studies; Copy number; Copy number variations; Cross-Sectional Studies; Deoxyribonucleic acid; DNA; Female; Gastrointestinal Absorption - genetics; Gene Dosage; Genetic aspects; Glucose; Glucose metabolism; Glucose tolerance; Glucose Tolerance Test; Health aspects; Healthy Volunteers; High density lipoprotein; Homeostasis; Humans; Insulin; Insulin - metabolism; Insulin resistance; Insulin Resistance - genetics; Intra-Abdominal Fat - diagnostic imaging; Intra-Abdominal Fat - metabolism; Liver; Liver - metabolism; Magnetic Resonance Imaging; Male; Metabolic syndrome; Metabolism; Multivariate analysis; Physiological aspects; Polymerase chain reaction; Salivary alpha-Amylases - genetics; Starch; Starch - administration & dosage
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa473

Abstract 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.