Yuwei Liu1,2, Caren E Smith1, Laurence D Parnell3, Yu-Chi Lee1, Ping An4, Robert J Straka5, Hemant K Tiwari6, Alexis C Wood7, Edmond K Kabagambe8, Bertha Hidalgo9, Paul N Hopkins10, Michael A Province4, Donna K Arnett11, Katherine L Tucker12, Jose M Ordovas1,13,14, Chao-Qiang Lai3. 1. Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA. 2. School of Public Health, Fudan University, Shanghai, China. 3. USDA Agricultural Research Service, Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA. 4. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO. 5. Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN. 6. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL. 7. USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX. 8. Department of Medicine, Vanderbilt University, Nashville, TN. 9. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL. 10. Division of Cardiovascular Medicine, University of Utah, Salt Lake City, UT. 11. College of Public Health, University of Kentucky, Lexington, KY. 12. Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA. 13. IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain. 14. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Abstract
BACKGROUND: Copy number variation (CNV) in the salivary amylase gene (AMY1) modulates salivary α-amylase levels and is associated with postprandial glycemic traits. Whether AMY1-CNV plays a role in age-mediated change in insulin resistance (IR) is uncertain. METHODS: We measured AMY1-CNV using duplex quantitative real-time polymerase chain reaction in two studies, the Boston Puerto Rican Health Study (BPRHS, n = 749) and the Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN, n = 980), and plasma metabolomic profiles in the BPRHS. We examined the interaction between AMY1-CNV and age by assessing the relationship between age with glycemic traits and type 2 diabetes (T2D) according to high or low copy numbers of the AMY1 gene. Furthermore, we investigated associations between metabolites and interacting effects of AMY1-CNV and age on T2D risk. RESULTS: We found positive associations of IR with age among subjects with low AMY1-copy-numbers in both studies. T2D was marginally correlated with age in participants with low AMY1-copy-numbers but not with high AMY1-copy-numbers in the BPRHS. Metabolic pathway enrichment analysis identified the pentose metabolic pathway based on metabolites that were associated with both IR and the interactions between AMY1-CNV and age. Moreover, in older participants, high AMY1-copy-numbers tended to be associated with lower levels of ribonic acid, erythronic acid, and arabinonic acid, all of which were positively associated with IR. CONCLUSIONS: We found evidence supporting a role of AMY1-CNV in modifying the relationship between age and IR. Individuals with low AMY1-copy-numbers tend to have increased IR with advancing age. Published by Oxford University Press on behalf of the American Association for Clinical Chemistry 2020. This work is written by US Government employees and is in the public domain in the US.
BACKGROUND: Copy number variation (CNV) in the salivary amylase gene (AMY1) modulates salivary α-amylase levels and is associated with postprandial glycemic traits. Whether AMY1-CNV plays a role in age-mediated change in insulin resistance (IR) is uncertain. METHODS: We measured AMY1-CNV using duplex quantitative real-time polymerase chain reaction in two studies, the Boston Puerto Rican Health Study (BPRHS, n = 749) and the Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN, n = 980), and plasma metabolomic profiles in the BPRHS. We examined the interaction between AMY1-CNV and age by assessing the relationship between age with glycemic traits and type 2 diabetes (T2D) according to high or low copy numbers of the AMY1 gene. Furthermore, we investigated associations between metabolites and interacting effects of AMY1-CNV and age on T2D risk. RESULTS: We found positive associations of IR with age among subjects with low AMY1-copy-numbers in both studies. T2D was marginally correlated with age in participants with low AMY1-copy-numbers but not with high AMY1-copy-numbers in the BPRHS. Metabolic pathway enrichment analysis identified the pentose metabolic pathway based on metabolites that were associated with both IR and the interactions between AMY1-CNV and age. Moreover, in older participants, high AMY1-copy-numbers tended to be associated with lower levels of ribonic acid, erythronic acid, and arabinonic acid, all of which were positively associated with IR. CONCLUSIONS: We found evidence supporting a role of AMY1-CNV in modifying the relationship between age and IR. Individuals with low AMY1-copy-numbers tend to have increased IR with advancing age. Published by Oxford University Press on behalf of the American Association for Clinical Chemistry 2020. This work is written by US Government employees and is in the public domain in the US.
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