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Title: Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption
Authors: Corella, Dolores
Ortega-Azorín, Carolina
Sorlí, José V.
Covas, María Isabel
Carrasco, Paula
Salas-Salvadó, Jordi
Martínez-González, Miguel Ángel
Arós, Fernando
Lapetra, José
Serra-Majem, Lluis 
Lamuela-Raventós, R.M.
Gómez-Gracia, Enrique
Fiol, Miquel
Pinto, Xavier
Ros, Emilio
Martí, Amelia
Coltell, Oscar
Coltell, Oscar
Ordovás, José M.
Estruch, Ramón
UNESCO Clasification: 3206 Ciencias de la nutrición
Keywords: Mediterranean diet
Physical activity
Obesity, et al
Issue Date: 2012
Project: Red Alimentación Saludable en la Prevención Primaria de Enfermedades Crónicas: la Red Predimed. (Retics 2006) 
Journal: PLoS ONE 
Abstract: Background: Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. Objective: To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake. Methods: Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed. Results: FTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (P<0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR=1.07; 95%CI 1.01-1.13). We found relevant statistical interactions (P<0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P=0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P=0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/-SE: -0.57+/-0.16 g/d per-score-allele; P=0.001). Conclusion: Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI.
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0052344
Source: PLoS ONE [ISSN 1932-6203], v. 7(12)
Rights: by-nc-nd
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