Contribution of Common Genetic Variants to Obesity and Obesity-Related Traits in Mexican Children and Adults

Paola León-Mimila,Hugo Villamil-Ramírez,Roxana Gutiérrez-Vidal,Carlos Posadas-Romeros,Samuel Canizales-Quinteros,Blanca Del Río-Navarro,Victor Acuña-Alonzo,Leonor Jacobo-Albavera,Teresa Villarreal-Molina,Joel Vega-Badillo,Sandra Romero-Hidalgo,Adrián Canizalez-Román,Blanca López-Contreras,Francisco Campos-Pérez,Marisela Villalobos-Comparán,Carlos Aguilar-Salinas

doi:10.1371/journal.pone.0070640

Abstract

BackgroundSeveral studies have identified multiple obesity-associated loci mainly in European populations. However, their contribution to obesity in other ethnicities such as Mexicans is largely unknown. The aim of this study was to examine 26 obesity-associated single-nucleotide polymorphisms (SNP) in a sample of Mexican mestizos.Methods9 SNPs in biological candidate genes showing replications (PPARG, ADRB3, ADRB2, LEPR, GNB3, UCP3, ADIPOQ, UCP2, and NR3C1), and 17 SNPs in or near genes associated with obesity in first, second and third wave GWAS (INSIG2, FTO, MC4R, TMEM18, FAIM2/BCDIN3, BDNF, SH2B1, GNPDA2, NEGR1, KCTD15, SEC16B/RASAL2, NPC1, SFRF10/ETV5, MAF, PRL, MTCH2, and PTER) were genotyped in 1,156 unrelated Mexican-Mestizos including 683 cases (441 obese class I/II and 242 obese class III) and 473 normal-weight controls. In a second stage we selected 12 of the SNPs showing nominal associations with obesity, to seek associations with quantitative obesity-related traits in 3 cohorts including 1,218 Mexican Mestizo children, 945 Mexican Mestizo adults, and 543 Indigenous Mexican adults.ResultsAfter adjusting for age, sex and admixture, significant associations with obesity were found for 6 genes in the case-control study (ADIPOQ, FTO, TMEM18, INSIG2, FAIM2/BCDIN3 and BDNF). In addition, SH2B1 was associated only with class I/II obesity and MC4R only with class III obesity. SNPs located at or near FAIM2/BCDIN3, TMEM18, INSIG2, GNPDA2 and SEC16B/RASAL2 were significantly associated with BMI and/or WC in the combined analysis of Mexican-mestizo children and adults, and FTO locus was significantly associated with increased BMI in Indigenous Mexican populations.ConclusionsOur findings replicate the association of 8 obesity-related SNPs with obesity risk in Mexican adults, and confirm the role of some of these SNPs in BMI in Mexican adults and children.

Highlights

The prevalence of obesity is rapidly increasing worldwide [1]
Using a case control design, we sought to assess the contribution of two different sets of single-nucleotide polymorphisms (SNP) with obesity in Mexican Mestizo adults: 9 SNPs in biological candidate genes showing replications in at least 10 studies (PPARG, ADRB3, ADRB2, LEPR, GNB3, UCP3, ADIPOQ, UCP2, and NR3C1) [5] and 17 SNPs in or near genes associated with obesity in first, second and third wave genome-wide association studies (GWAS) (INSIG2, FTO, MC4R, TMEM18, FAIM2/BCDIN3, BDNF, SH2B1, GNPDA2, NEGR1, KCTD15, SEC16B/RASAL2, NPC1, SFRF10/ETV5, MAF, PRL, MTCH2, and PTER) [12,13,14,15,16,17,18]
2 of the 8 SNPs previously associated with obesity using this approach showed significant association in the Mexican population

Summary

Introduction

According to the 2012 National Health and Nutrition Survey in the Mexican population, the prevalence of overweight and obesity is 71.2% in adults aged above 20 years and 34.4% in children [2]. Associations of many common genetic variants with obesity have been replicated mainly in several European and Asian populations [5,6] there are still few studies in the Mexican population [7,8,9,10]. Several studies have identified multiple obesity-associated loci mainly in European populations. Their contribution to obesity in other ethnicities such as Mexicans is largely unknown. The aim of this study was to examine 26 obesity-associated single-nucleotide polymorphisms (SNP) in a sample of Mexican mestizos

Objectives

Methods

Results

Discussion

Conclusion