Interaction between FTO rs9939609 and the Native American-origin ABCA1 rs9282541 affects BMI in the admixed Mexican population

Marisela Villalobos-Comparán,Bárbara Antuna-Puente,Osvaldo Erik Sánchez-Hernández,Juan Antonio González-Barrios,María Rocío Thompson-Bonilla,Martha Eunice Rodríguez-Arellano,Francisco Campos-Pérez,José Luis Merino-García,Paola León-Mimila,Hugo Villamil‐Ramírez ,Samuel Cañizales-Quinteros ,Teresa Villarreal-Molina ,Gilberto Vargas‐Alarcón ,Diego Jarquín ,Rafael Velázquez‐Cruz ,Carlos Posadas‐Romero ,Jorge Salmerón ,Alessandra Carnevale,Manuel Quiterio,Sandra Romero‐Hidalgo

doi:10.1186/s12881-017-0410-y

Abstract

BackgroundThe aim of this study was to explore whether interactions between FTO rs9939609 and ABCA1 rs9282541 affect BMI and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations.MethodsA total of 3938 adults and 636 school-aged children from Central Mexico were genotyped for both polymorphisms. Subcutaneous and visceral adipose tissue biopsies from 22 class III obesity patients were analyzed for FTO and ABCA1 mRNA expression. Generalized linear models were used to test for associations and gene-gene interactions affecting BMI, WC and FTO expression.ResultsFTO and ABCA1 risk alleles were not individually associated with higher BMI or WC. However, in the absence of the ABCA1 risk allele, the FTO risk variant was significantly associated with higher BMI (P = 0.043) and marginally associated with higher WC (P = 0.067), as reported in Europeans. The gene-gene interaction affecting BMI and WC was statistically significant only in adults. FTO mRNA expression in subcutaneous abdominal adipose tissue according to ABCA1 genotype was consistent with these findings.ConclusionsThis is the first report showing evidence of FTO and ABCA1 gene variant interactions affecting BMI, which may explain previously reported population differences. Further studies are needed to confirm this interaction.

Highlights

The aim of this study was to explore whether interactions between Fat mass and obesity associated gene (FTO) rs9939609 and ATP Binding cassette Transporter A-1 (ABCA1) rs9282541 affect Body mass index (BMI) and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations
In the overall analysis and under additive inheritance models, the FTO “A” risk allele was not significantly associated with higher BMI (β = 0.187, P = 0.143) or higher WC (β = 0.409, P = 0.208), nor was the ABCA1 “T” risk allele associated with BMI or WC (β = 0.247, P = 0.154 and β = 0.369, P = 0.403, respectively)
High Density Lipoprotein Cholesterol (HDL-C) levels were higher in FTO “A” homozygous individuals, the association did not reach statistical significance (β = 0.005, P = 0.097)

Summary

Introduction

The aim of this study was to explore whether interactions between FTO rs9939609 and ABCA1 rs9282541 affect BMI and waist circumference (WC), and could explain previously reported population differences in FTO-obesity and FTO-BMI associations in the Mexican and European populations. The ABCA1-R230C variant (rs9282541) is an ancestry-specific polymorphism private to the Americas and has been strongly associated with low HDLcholesterol (HDL-C), its association with BMI and obesity is inconsistent [6,7,8]. This allele is of particular interest, because it is relatively frequent in the Mexican mestizo population (0.11), is functional and was found to interact with BMI affecting abdominal fat distribution in Mexican premenopausal women [8]. The aim of this study was to analyze possible FTO rs9939609 - ABCA1 rs9282541 interactions affecting BMI, waist circumference (WC) and HDL-C levels in individuals from Central Mexico, which could help explain the differences observed between this and European populations

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