(OR02-06-23) Carbohydrate Digestion-Related AMY1 Gene Copy Number Variations As Determinants of Novel Metabolomics Signatures Related to Type 2 Diabetes

Saturday, July 22, 2023

3:30 PM – 3:42 PM ET

Location: Constitution B

Presenting Author(s)

YH

Yoriko Heianza, RD, PhD (she/her/hers)

Research Assistant Professor
Tulane University School of Public Health and Tropical Medicine
New Orleans, Louisiana, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

RS

Ryousuke Satou

Tulane University
YL

Yadan Li

School of Public Health and Tropical Medicine, Tulane University
AK

Akemi Katsurada

Tulane University
XW

Xuan Wang

School of Public Health and Tropical Medicine, Tulane University
JC

Jing Chen

School of Public Health and Tropical Medicine, Tulane University
FS

Frank M. Sacks, MD

Harvard T.H. Chan School of Public Health
Boston, Massachusetts, United States
JH

Jiang He, MD, PhD

School of Public Health and Tropical Medicine, Tulane University
New Orleans, Louisiana, United States
TK

Tanika Kelly

College of Medicine, University of Illinois at Chicago
LB

Lydia Bazzano, MD, PhD, MPH

Tulane University School of Public Health and Tropical Medicine
New Orleans, Louisiana, United States
LQ

Lu Qi, MD, PhD

Tulane University School of Public Health and Tropical Medicine
New Orleans, Louisiana, United States

Disclosure(s):

Yoriko Heianza, RD, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Carbohydrates comprise the majority of energy intake of most diets and have a substantial effect on glucose metabolism. Dietary carbohydrates in the form of polysaccharides are digested by amylases into monomers and are absorbed into the systemic circulation. Salivary amylase is encoded by the AMY1 gene, and copy number variation (CNV) in the AMY1 gene region has been recently found to be a genetic determinant of individual differences in the extent of carbohydrate digestion. Associations of AMY1 CNVs with carbohydrate metabolism and interconnected pathways, such as lipids and energy metabolism, remain underdetermined. We therefore aimed to investigate associations of AMY1 CNVs with various circulating metabolites related to the risk of type 2 diabetes in the metabolic pathways of carbohydrate, energy, and lipids.

Methods: This study included 144 adults from the Bogalusa Heart Study. We measured AMY1 copy number (CN) using the digital droplet PCR approach. Serum concentrations of protein AMY1 were also measured. High or low AMY1 CN was based on a median value; logistic regression analysis was performed to identify the significant metabolites related to high AMY1 CN. Circulating metabolites were measured by untargeted, ultra-high-performance LC-MS metabolomics profiling.

Results: Higher AMY1 CN was related to higher concentrations of protein AMY1 in serum (Pearson Correlation coefficient=0.43; p < .0001). Higher AMY1 CN was related to lower blood glucose (p=0.02). Circulating levels of metabolites in carbohydrate pathways (such as glucose, fructose, and mannose) were significantly associated with high CN in results of the logistic regression. Other metabolites in the interconnected pathways of carbohydrate metabolism, such as citrate in the TCA cycle, hexosylceramides, lactosylceramides, and sphingomyelins were also significantly associated with high AMY1 CN.

Conclusions: Genetically determined variation in carbohydrate digestion, assessed by AMY1 CNVs, was significantly associated with individual differences in metabolomics signatures related to the risks of type 2 diabetes and cardiovascular disease. These results suggest novel pathways linking carbohydrate digestion and cardiometabolic diseases.

Funding Sources: National Institute of General Medical Sciences