Association of FTO, ABCA1, ADRB3, and PPARG variants with obesity, type 2 diabetes, and metabolic syndrome in a Northwest Mexican adult population
Introduction
Non-communicable diseases related to metabolism, such as obesity, type 2 diabetes (T2D), and metabolic syndrome are a major global public health problem of the 21st century, with obesity being particularly important because it is the most frequent. The worldwide prevalence of obesity has increased considerably in recent years in adults and children; nearly 40% of adults are classed as overweight and 10–15% are obese.1 In Mexico, the prevalence of non-communicable diseases is continuously increasing. According to the 2018 National Health and Nutrition Survey in the Mexican population, the prevalence of adults classified as overweight and obese was 75.2% (71.3% in 2012), whereas the prevalence of T2D was 10.3% (9.2% in 2012).2
Various environmental factors are associated with obesity, T2D, and metabolic syndrome including those related to lifestyle (diet or level of activity), gut microbiota and its composition, and genetic alterations as single nucleotide polymorphisms (SNPs).3., 4. The advent of genome-wide association studies (GWAS) has led to revelations of numerous SNPs being associated with differences in anthropometrical or biochemical traits, or associated with metabolic diseases. However, genetic variation identified to date explains only a small fraction (5–10%) of genetic variance. More than 120 genes have been demonstrated to be associated with obesity, predominantly in European populations.5 Fat mass and obesity-associated gene (FTO) variants are some of the most studied SNPs globally, and have a strong association with obesity. SNPs in ABCA1 and PPARG have also been linked with metabolic diseases. ABCA1 is highly expressed in the liver and adipose tissues, and its expression is important in mobilizing adipose tissue cholesterol for transport to the liver for excretion, whereas PPARG is related to adipogenesis regulation. In contrast, ADBR3 is a beta-adrenergic receptor which could participate in the development of metabolic diseases, such as T2D (participating in insulin sensitivity) or obesity (control of fatty acid storage and release in adipose tissue).6
Alleles from FTO, ABCA1, ADRB3, and PPARG have been associated with obesity in some Mexican populations, predominantly those from Central Mexico.7., 8. Due to nutritional differences among Northwest of Mexico and Central Mexico subjects (higher consumption of red meat and simple carbohydrates in Northwest of Mexico2) and the important participation of FTO, ABCA1, ADBR3, and PPARG in the development of metabolic diseases (obesity, T2D, and metabolic syndrome) in several populations, the study of these allelic variants in Northwest Mexican adult population is important to assess their contribution to these phenotypes. The aim of this work was to identify associations among FTO rs9939609 A-allele, ABCA1 rs9282541 A-allele, ADRB3 rs4994 G-allele, and PPARG rs1801282 G-allele with metabolic diseases such as obesity, T2D, or metabolic syndrome in a population from Northwest Mexico.
Section snippets
Population-based study
Sample size was estimated for the association between FTO rs9939609 and obesity in a cases-control design considering an additive model with an allele frequency of 0.23, the frequency reported in individuals of Mexican Ancestry in Los Angeles from the 1000 genomes project, with the Genetic Association Study Power Calculator, with alpha set at 0.05. For a power of 80%, 250 normal weight and 250 obese subjects were required to detect an allelic odds ratio of 1.35. Blood samples were taken from
Characteristics of the study population
The study population comprised 846 individuals from Sinaloa state. Of these, 266 were classified as normal weight, 285 with obesity (without T2D), and 295 with T2D. Of all the subjects with obesity and T2D, 62% (365 people) were classified with metabolic syndrome. The biochemical and anthropometrical parameters measured in the study participants are shown in Table 1. Most parameters including age, weight, BMI, waist circumference, hip circumference, arterial pressure, total cholesterol, and
Discussion
This study demonstrated that allelic variants of the genes FTO rs9939609 A-allele was associated with obesity and metabolic syndrome and the presence of all four SNPs together was associated with obesity. However, the individual presences of SNPs (ABCA1, ADRB3, and PPARG) were not associated with metabolic diseases in Northwest Mexican adult population.
The presence of SNPs may be associated with metabolic diseases such as obesity, T2D, and metabolic syndrome, obesity is the most important of
Conclusions
This study provides the evidence that the individual presence of FTO rs9939609 A-allele could participate in development of obesity or metabolic syndrome. Additionally, our cumulative risk analysis supports the influence of FTO rs9939609 A-allele, ABCA1 rs9282541 A-allele, ADRB3 rs4994 G-allele, and PPARG rs1801282 G-allele as a genetic risk factor in obesity. Lastly, this study shows evidence of the importance of studying network models of genes in metabolic diseases, which could help to
CRediT authorship contribution statement
Jorge Velazquez-Roman: Data curation, Writing-Original draft preparation, conceptualization; Uriel A. Angulo-Zamudio: Visualization, Investigation, Methodology; Julio Medina-Serranod and Nora DeLira-Bustillo: Formal analysis, Data curation; Hugo Villamil-Ramírez and Samuel Canizales-Quinteros: Writing- Reviewing and Editing; Nidia Leon-Sicairos: Supervision and Reviewing; Abraham Campos-Romerog and Jonathan Alcántar-Fernández: Software, Validation and Reviewing; Adrian Canizalez-Roman:
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
We would like to thank Guadron-Llanos Alma for logistic support during the final phase of the sampling process.
Funding
This work was supported by PROFAPI-UAS (grants numbers 2013/202, 2014/227 and 2015/298) and PRODEP-SEP (grants numbers 2014 DSA/103.5/14/11063-, FOLIO UAS-PTC-121) to J.V.R.
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