REV-ERB-ALPHA circadian gene variant associates with obesity in two independent populations: Mediterranean and North American

Abstract

Scope: Despite the solid connection between REV-ERB and obesity, the information about whether genetic variations at this locus may be associated with obesity traits is scarce. Therefore our objective was to study the association between REV-ERB-ALPHA1 rs2314339 and obesity in two independent populations.

Methods and results: Participants were 2214 subjects from Spanish Mediterranean (n = 1404) and North American (n = 810) populations. Anthropometric, biochemical, dietary, and genotype analyses were performed. We found novel associations between the REV-ERB-ALPHA1 rs2314339 genotype and obesity in two independent populations: in Spanish Mediterranean and North American groups, the frequency of the minor-allele-carriers (AA+ AG) was significantly lower in the "abdominally obese" group than in those of the "nonabdominally obese" group (p < 0.05). Minor allele carriers had lower probability of abdominal obesity than noncarriers, and the effect was of similar magnitude for both populations (OR ≈ 1.50). There were consistent associations between REV-ERB-ALPHA1 genotype and obesity-related traits (p < 0.05). Energy intake was not significantly associated with REV-ERB-ALPHA1 rs2314339. However, physical activity significantly differed by genotype. A significant interaction between the REV-ERB-ALPHA1 variant and monounsaturated-fatty-acids (MUFA) intake for obesity was also detected in the Mediterranean population.

Conclusion: This new discovery highlights the importance of REV-ERB-ALPHA1 in obesity and provides evidence for the connection between our biological clock and obesity-related traits.

Keywords: Circadian; Clock genes; Obesity; REV-ERB-ALPHA-1; Single nucleotide Polymorphism.

Conflict of interest statement

The authors have declared no conflict of interest.

© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Figures

Figure 1

Association of REV-ERB-ALPHA1 genotype with obesity-related traits in the Mediterranean population.

Figure 2

Mean (SE) BMI by rs2314339 polymorphism at the REV-ERB-ALPHA1 gene according to MUFA intakes below and above the population median (55 percentage of total fat). Estimated means were adjusted for sex, age, and nutrition centre. p Values for the interaction (p = 0.014) terms between fat intake and the rs2314339 polymorphism were obtained in the hierarchical multivariate interaction model containing MUFA intake as a categorical variable with additional control for the other covariates.

Figure 3

Association of REV-ERB-ALPHA1 genotype with PA in both populations Mediterranean and North American.