Salivary AMY1 Copy Number Variation Modifies Age-Related Type 2 Diabetes Risk

Yuwei Liu, Caren E. Smith, Laurence D. Parnell, Yu Chi Lee, Ping An, Robert J. Straka, Hemant K. Tiwari, Alexis C. Wood, Edmond K. Kabagambe, Bertha Hidalgo, Paul N. Hopkins, Michael A. Province, Donna K. Arnett, Katherine L. Tucker, Jose M. Ordovas, Chao Qiang Lai

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish
Pages (from-to)718-726
Number of pages9
JournalClinical chemistry
Issue number5
StatePublished - May 1 2020


  • AMY1 copy numbers
  • age
  • insulin resistance
  • salivary amylase


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