Salivary AMY1 copy number variation modifies age-related type 2 diabetes risk

Authors: LIU, YUWEI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Parnell, Laurence; LEE, YU-CHI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; AN, PING - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; STRAKA, ROBERT - University Of Minnesota; TIWARI, HEMANT - University Of Alabama At Birmingham; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); KABAGAME, EDMOND - Vanderbilt University; HOPKINS, PAUL - University Of Utah; PROVINCE, MICHAEL - Washington University; ARNETT, DONNA - University Of Kentucky; TUCKER, KATHERINE - University Of Massachusetts; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Lai, Chao Qiang

Submitted to: Clinical Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/28/2020
Publication Date: 4/26/2020
Citation: Liu, Y., Smith, C.E., Parnell, L.D., Lee, Y., An, P., Straka, R.J., Tiwari, H.K., Wood, A.C., Kabagame, E.K., Hopkins, P., Province, M., Arnett, D.K., Tucker, K., Ordovas, J.M., Lai, C. 2020. Salivary AMY1 copy number variation modifies age-related type 2 diabetes risk. Clinical Chemistry. 66(5):718-726. https://doi.org/10.1093/clinchem/hvaa072.
DOI: https://doi.org/10.1093/clinchem/hvaa072

Interpretive Summary: Starchy foods are a major source of dietary carbohydrates and contribute significantly to the energy intake of Americans. Salivary a-amylase is an enzyme that initiates, in the mouth, the digestion of polysaccharides in starch into simpler sugars, such as glucose. This enzyme is encoded by the AMY1 gene, and previous research has found that this gene is present in multiple numbers of copies that vary dramatically among individuals. The presence of low AMY1 copy numbers has been associated with decreased salivary a-amylase activity and, in some cases, with increased risk of obesity and type 2 diabetes (T2D). However, these associations have not been investigated in the context of aging; which is usually associated with a decline in the tolerance to high intake of carbohydrates, resulting in an increased risk of T2D. We investigated the role of AMY1 copy numbers in determining the risk of T2D as we age in two different populations, one predominantly White and another one Hispanic. Our study showed that insulin resistance and the risk of T2D were positively associated with age only for those persons with low-AMY1 copy numbers. These results support the notion that individuals with low AMY1 copy number and with high consumption of starchy foods may have a higher likelihood of developing insulin resistance with advancing age, and hence increased risk of T2D.

Technical Abstract: Background: Whether the copy number variation (CNV) in the salivary amylase gene (AMY1), which modulates salivary a-amylase level and postprandial glycemic traits, plays a role in age-mediated change in insulin resistance is unknown. Methods: We measured AMY1 CNV using duplex quantitative real-time polymerase chain reaction (qPCR) in two study populations: Boston Puerto Rican Health Study (BPRHS; n = 749) and Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN; n = 980) and plasma metabolome profiles in BPRHS. We examined the relationship between age and glycemic traits and type 2 diabetes according to the high or low copy number of AMY1 gene using a linear regression model, and link between metabolites and interaction between AMY1 CNV and age on diabetes risk. Results: In two independent populations (BPRHS and GOLDN), we observed positive associations of fasting glucose with age in individuals, regardless of AMY1 CNV, while HOMA-IR was positively associated with age only among participants with low-AMY1 copy numbers. Type 2 diabetes prevalence was marginally correlated with age in participants with low-AMY1 copy numbers, but not with those of high-AMY1 copy numbers in BPRHS. Metabolic pathway enrichment analysis highlighted pentose metabolic pathways were associated with the interactions between AMY1 copy number and age. In older participants, high AMY1 copy number tended to be associated with lower concentrations of ribonic acid, erythronic acid and arabinonic acid which were positively associated with HOMA-IR. Conclusions: Our results suggest a role for AMY1 copy number in modifying the relation between age and insulin resistance. Individuals with low AMY1 copy number may have a higher likelihood of developing insulin resistance with advancing age.