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

Clara Marquina,Barbora De Courten,Regina Belski,Negar Naderpoor,Harry Banaharis,Aya Mousa

doi:10.3390/jcm8030382

Clara Marquina, Barbora De Courten + Show 4 more

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https://doi.org/10.3390/jcm8030382

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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.

Highlights

Obesity is a multifactorial disorder that leads to an increased risk of cardiometabolic diseases including type 2 diabetes mellitus (T2DM) and cardiovascular diseases
Two previous studies reported that increased fat mass, as measured by gold-standard dual energy X-ray absorptiometry (DEXA), was associated with low AMY1 copy number variations (CNVs) in Scandinavian populations [9,16], which is consistent with our findings
We report a significantly higher low-density lipoprotein (LDL) cholesterol concentration in low AMY1 carriers compared with high AMY1 carriers, which persisted after adjusting for age, sex, and fat mass, as well as in exploratory analyses adjusted for dietary factors

Summary

Introduction

Obesity is a multifactorial disorder that leads to an increased risk of cardiometabolic diseases including type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The prevalence of obesity has tripled since 1975, and is expected to continue increasing [1]. Gaining a better understanding of the underlying risk factors of obesity is crucial for developing effective prevention and management strategies. It is well recognised, based on family and twin studies, that body mass index (BMI) is a highly heritable trait, with between 40–70% of its variance being attributable to genetic factors [2]. The common genetic variants identified in genome-wide association studies account for only a small proportion of population variability [2]. Copy number variations (CNVs) in the salivary α-amylase gene AMY1 have emerged as potential contributors to this heritability

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