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

Author
item GARAULET, MARTA - Universidad De Murcia
item SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item GOMEZ-ABELLAN, PURIFICACION - Universidad De Murcia
item ORDOVA S-MONTANES, MARIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LEE, YU-CHI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Parnell, Laurence
item ARNETT, DONNA - University Of Alabama
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/21/2013
Publication Date: 4/1/2014
Citation: Garaulet, M., Smith, C.E., Gomez-Abellan, P., Ordova S-Montanes, M., Lee, Y., Parnell, L.D., Arnett, D.K., Ordovas, J.M. 2014. REV-ERB-ALPHA circadian gene variant associates with obesity in two independent populations: Mediterranean and North American. Molecular Nutrition and Food Research. 58(4):821-829.

Interpretive Summary: The molecular paths leading to obesity are complex and scores of proteins have been involved in the predisposition and expression of this disease. One of them is known as REV-ERB, which is also a component of our biological clock; however, despite the functional connection between this protein and obesity, there is very little knowledge regarding the association between its genetic variation and obesity traits. Therefore our objective was to study the association between a common variant (rs2314339) at this gene and obesity in two independent populations in North America and Europe (n=2214). We found that this genetic variant was less common in the obese group than in the non-obese group. Energy intake was not significantly associated with the polymorphism (DNA sequence variation). However, physical activity significantly differed by genotype, suggesting that the relation between this gene and obesity may be driven by physical activity rather than nutritional factors.

Technical Abstract: 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. 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 approx. 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. 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.