Increased Inflammation and Cardiometabolic Risk in Individuals with Low AMY1 Copy Numbers

Abstract

Lower copy number variations (CNVs) in the salivary amylase gene (AMY1) have been associated with obesity and insulin resistance; however, the relationship between AMY1 and cardiometabolic risk has not been fully elucidated. Using gold-standard measures, we aimed to examine whether AMY1 CNVs are associated with cardiometabolic risk factors in an overweight or obese, otherwise healthy population. Fifty-seven adults (58% male) aged 31.17 ± 8.44 years with a body mass index (BMI) ≥25 kg/m2 were included in the study. We measured AMY1 CNVs (qPCR); anthropometry (BMI; body composition by dual-energy X-ray absorptiometry); cardiovascular parameters (blood pressure, serum lipids by ELISA); insulin sensitivity (hyperinsulinaemic–euglycaemic clamp), insulin secretion (intravenous glucose tolerance test), and serum inflammation markers (multiplex assays). Based on previous studies and median values, participants were divided into low (≤4) and high (>4) AMY1 CNV groups. Low AMY1 carriers (n = 29) had a higher fat mass (40.76 ± 12.11 versus 33.33 ± 8.50 kg, p = 0.009) and LDL-cholesterol (3.27 ± 0.80 versus 2.87 ± 0.69 mmol/L, p = 0.038), and higher serum levels of interleukin [IL]-6, IL-1β, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 (MCP-1) (all p < 0.05) compared with high AMY1 carriers (n = 28), but there were no differences in glycaemic measures, including insulin sensitivity or secretion (all p > 0.1). Except for MCP-1, the results remained significant in multivariable models adjusted for age, sex, and fat mass (all p < 0.05). Our findings suggest that low AMY1 CNVs are associated with increased cardiovascular disease risk and inflammation, but not glucose metabolism, in overweight or obese adults.