776-P: Low AMY1 Copy Number Variations Are Associated with Cardiometabolic Risk Factors in Overweight or Obese Adults

Background: Low serum amylase has been implicated in the pathogenesis of obesity and insulin resistance. Copy number variations (CNVs) in the salivary amylase gene (AMY1) correlate with serum amylase, and CNVs <4 have been associated with a higher risk of obesity and insulin resistance. However, the relationship between AMY1 and cardiometabolic risk has not been fully elucidated.

Objective: To examine whether AMY1 CNVs are associated with cardiometabolic risk factors.

Methods: In overweight or obese (BMI >25kg/m²), otherwise healthy adults, we measured AMY1 copy numbers (qPCR); serum amylase (commercial assay); anthropometry (BMI; body composition by dual-energy X-ray absorptiometry); cardiovascular parameters (blood pressure, plasma lipids by ELISA); fasting and 2-h glucose levels post-75g oral glucose tolerance test (glucose oxidase method), insulin sensitivity (hyperinsulinemic-euglycemic clamp), insulin secretion (intravenous glucose tolerance test), and serum inflammation markers (LEGENDplex™, Biolegend).

Results: Fifty-nine adults (58% males) aged 31.27 ± 8.61 were included in the study. Based on previous studies and median values, participants were divided into low CNV and high CNV carrier groups for individuals with ≤4 and >4 AMY1 CNVs, respectively. Low AMY1 CNV carriers (n=29) had a higher BMI (32.65 ± 5.37 vs. 30.28 ± 3.51 kg/m², p = 0.04), % fat mass (40.76 ± 12.22 vs. 33.13 ± 8.60%, p = 0.008), and LDL-c (3.25 ± 0.80 vs. 2.87 ± 0.63 mmol/L, p = 0.04) compared with the high AMY1 CNV group (n=30), as well as higher levels of interleukins [IL]-6, -1β, -10, and tumor necrosis factor-alpha (all p<0.05). Results remained significant after adjustment for age and sex. There were no differences between AMY1 CNV groups in glycaemic outcomes including insulin sensitivity or secretion as well as fasting and 2-hour glucose post-OGTT (p>0.1).

Conclusions: Our results suggest that low AMY1 CNVs are associated with increased obesity, cardiovascular risk, and inflammation.