Low Salivary Amylase Gene (AMY1) Copy Number Is Associated with Obesity and Gut Prevotella Abundance in Mexican Children and Adults.

Paola León-Mimila,Hugo Villamil-Ramírez,Carlos Aguilar-Salinas,Samuel Canizales-Quinteros,Blanca López-Contreras,Víctor Acuña-Alonzo,Rafael Velazquez-Cruz,Luis Macias-Kauffer,Sofía Morán-Ramos,Teresa Villarreal-Molina,Jorge Salmerón,Blanca Del Río-Navarro

doi:10.3390/nu10111607

Abstract

Genome-wide association studies (GWAS) have identified copy number variants (CNVs) associated with obesity in chromosomal regions 1p31.1, 10q11.22, 11q11, 16p12.3, and recently 1p21.1, which contains the salivary amylase gene (AMY1). Recent evidence suggests this enzyme may influence gut microbiota composition through carbohydrate (mainly starch) degradation. The role of these CNVs in obesity has been scarcely explored in the Latino population, and thus the aim of our study was to evaluate the association of 1p31.1, 10q11.22, 11q11, 16p12.3 and 1p21.1 CNVs with obesity in 921 Mexican children, to replicate significant associations in 920 Mexican adults, and to analyze the association of AMY1 copy number with gut microbiota in 75 children and 45 adults. Of the five CNVs analyzed, 1q11 CNV was significantly associated with obesity in children, but not in adults. Only AMY1 CNV was significantly associated with obesity in both age groups. Moreover, gut microbiota analyses revealed a positive correlation between AMY1 copy number and Prevotella abundance. This genus has enzymes and gene clusters essential for complex polysaccharide degradation and utilization. To our knowledge, this is the first study to analyze the association of these five CNVs in the Mexican population and to report a correlation between AMY1 CN and gut microbiota in humans.

Highlights

Obesity represents a major global health problem [1]
The role of CNVs in obesity has been scarcely explored in the Mexican population, and the aim of our study was to evaluate the association of five candidate copy number variants (1p31.1, 10q11.22, 11q11, 16p12.3 and 1p21.1) with obesity in Mexican children, to replicate significant associations in Mexican adults, and to analyze the association of AMY1 copy number with gut genera and species belonging to Enterobacteriaceae and Prevotellaceae families and their role in obesity in Mexican children and adults
Receptor Class C Group 5 Member B), 11q11/OR4P4/OR4S2/OR4C6, 16p12.3/NPY4R

Summary

Introduction

Obesity represents a major global health problem [1]. In Mexico, according to the NationalHealth and Nutrition Survey, the prevalence of overweight and obesity is 33.2% in children and72.5% in adults [2]. More than 90 single nucleotide polymorphism (SNPs) have been associated with body mass index (BMI) mainly in Caucasian populations [6,7,8,9,10,11], some of which were associated with BMI in Mexican children and adults [12]. It has been suggested that copy number variation (CNV) might contribute to explain the missing heritability of obesity [13] In this regard, genome-wide association studies (GWAS) have revealed certain CNV regions associated with obesity in European and Asian populations, including chromosomal regions

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