Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
School of Public Health, Fudan University, Shanghai, China.
Clin Chem. 2020 May 1;66(5):718-726. doi: 10.1093/clinchem/hvaa072.
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.
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.
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.
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.
唾液淀粉酶基因（AMY1）的拷贝数变异（CNV）调节唾液α-淀粉酶水平，并与餐后血糖特征相关。AMY1-CNV 是否在年龄介导的胰岛素抵抗（IR）变化中起作用尚不确定。
我们在两项研究中使用双定量实时聚合酶链反应测量 AMY1-CNV，即波士顿波多黎各健康研究（BPRHS，n=749）和降脂药物和饮食网络研究的遗传学（GOLDN，n=980），并在 BPRHS 中测量血浆代谢组学图谱。我们通过根据 AMY1 基因的高或低拷贝数评估年龄与血糖特征和 2 型糖尿病（T2D）之间的关系，来检查 AMY1-CNV 与年龄之间的相互作用。此外，我们研究了代谢物与 AMY1-CNV 和年龄对 T2D 风险的相互作用之间的关联。
我们发现，在两项研究中，低 AMY1 拷贝数的受试者中，IR 与年龄呈正相关。在 BPRHS 中，低 AMY1 拷贝数的参与者中，T2D 与年龄呈边缘相关，但高 AMY1 拷贝数的参与者中则没有相关性。代谢途径富集分析基于与 IR 和 AMY1-CNV 与年龄的相互作用均相关的代谢物，确定了戊糖代谢途径。此外，在年龄较大的参与者中，高 AMY1 拷贝数与核糖酸、赤藓糖和阿拉伯糖水平降低有关，所有这些代谢物均与 IR 呈正相关。
我们发现了支持 AMY1-CNV 在调节年龄与 IR 之间关系的作用的证据。低 AMY1 拷贝数的个体随着年龄的增长，IR 往往会增加。
