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.

Low AMY1 Copy Number Is Cross‐Sectionally Associated to an Inflammation‐Related Lipidomics Signature in Overweight and Obese Individuals

“…Serum amylase enzyme levels had a close positive association with the AMY1 copy number variation ( R = 0.54, P < 0.001) (Figure 1b). Similar to our previous findings with the AMY1 copy number, [ 5 ] we found a negative association between LDL‐C levels and the serum amylase concentrations in the present analysis ( R = −0.26, P = 0.05), but no associations with glucose‐related parameters. We also found negative associations between the AMY1 copy number and additional inflammatory cytokines (Figure 1c).…”

“…The baseline characteristics of the 57 participants according to the AMY1 copy number groups have been previously described. [ 5 ] The AMY1 copy number distribution had an estimated median copy number of 4, ranging from 1 to 13 ( Figure 1 a). Serum amylase enzyme levels had a close positive association with the AMY1 copy number variation ( R = 0.54, P < 0.001) (Figure 1b).…”

“…Among 57 adults with overweight and obesity, divided into low (≤4) and high (>4) AMY1 copies, we previously described that low AMY1 carriers ( n = 29) had higher fat mass, BMI, LDL‐cholesterol, and increased markers of chronic inflammation (IL6, IL1β, TNFα, MCP‐1) in plasma compared with high AMY1 carriers ( n = 28). [ 5 ] The results remained significant in multivariable models adjusted for age, sex, and fat mass. Thus, low AMY1 was associated with increased cardiovascular disease risk and inflammation.…”

“…[ 2,4 ] Hence, reduced AMY1 copy numbers have also been associated with increased body mass index (BMI), obesity and cardiovascular risk, IR, and inflammation in both adults and children. [ 2–8 ] However, the association between the AMY1 copy number and obesity has been challenged by recent studies that have found no significant associations despite having a strong statistical power. [ 9–12 ] These conflicting results could be partially attributed to differences in the starch intake.…”

“…Thus, low AMY1 was associated with increased cardiovascular disease risk and inflammation. [ 5 ] As previous metabolomic studies suggested an increased metabolic reliance on fatty acids in individuals with low AMY1 copy numbers, here, we decided to explore more in depth the lipidomic signatures of low and high AMY1 carriers in this well‐characterized cohort of overweight or obese but otherwise healthy individuals.…”