Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption

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 whet...

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Main Authors: Corella, D. (Dolores), Ortega-Azorin, C. (Carolina), Sorli, J.V. (Jose V.), Covas, M.I. (María Isabel), Carrasco, P. (Paula), Salas-Salvado, J. (Jordi), Martinez-Gonzalez, M.A. (Miguel Ángel), Aros, F. (Fernando), Lapetra, J. (José), Serra-Majem, L. (Luis), Lamuela-Raventos, R.M. (Rosa Maria), Gomez-Gracia, E. (Enrique), Fiol, M. (Miquel), Pinto, X. (Xavier), Ros, E. (Emilio), Marti-del-Moral, A. (Amelia), Coltell, O. (Oscar), Ordovas, J.M. (Jose Maria), Estruch, R. (Ramón)
Format: info:eu-repo/semantics/article
Language:eng
Published: Public Library of Science 2014
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Online Access:https://hdl.handle.net/10171/35531
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author Corella, D. (Dolores)
Ortega-Azorin, C. (Carolina)
Sorli, J.V. (Jose V.)
Covas, M.I. (María Isabel)
Carrasco, P. (Paula)
Salas-Salvado, J. (Jordi)
Martinez-Gonzalez, M.A. (Miguel Ángel)
Aros, F. (Fernando)
Lapetra, J. (José)
Serra-Majem, L. (Luis)
Lamuela-Raventos, R.M. (Rosa Maria)
Gomez-Gracia, E. (Enrique)
Fiol, M. (Miquel)
Pinto, X. (Xavier)
Ros, E. (Emilio)
Marti-del-Moral, A. (Amelia)
Coltell, O. (Oscar)
Ordovas, J.M. (Jose Maria)
Estruch, R. (Ramón)
author_facet Corella, D. (Dolores)
Ortega-Azorin, C. (Carolina)
Sorli, J.V. (Jose V.)
Covas, M.I. (María Isabel)
Carrasco, P. (Paula)
Salas-Salvado, J. (Jordi)
Martinez-Gonzalez, M.A. (Miguel Ángel)
Aros, F. (Fernando)
Lapetra, J. (José)
Serra-Majem, L. (Luis)
Lamuela-Raventos, R.M. (Rosa Maria)
Gomez-Gracia, E. (Enrique)
Fiol, M. (Miquel)
Pinto, X. (Xavier)
Ros, E. (Emilio)
Marti-del-Moral, A. (Amelia)
Coltell, O. (Oscar)
Ordovas, J.M. (Jose Maria)
Estruch, R. (Ramón)
author_sort Corella, D. (Dolores)
collection DSpace
description 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.
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spelling oai:dadun.unav.edu:10171-355312024-01-24T08:58:36Z Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption Corella, D. (Dolores) Ortega-Azorin, C. (Carolina) Sorli, J.V. (Jose V.) Covas, M.I. (María Isabel) Carrasco, P. (Paula) Salas-Salvado, J. (Jordi) Martinez-Gonzalez, M.A. (Miguel Ángel) Aros, F. (Fernando) Lapetra, J. (José) Serra-Majem, L. (Luis) Lamuela-Raventos, R.M. (Rosa Maria) Gomez-Gracia, E. (Enrique) Fiol, M. (Miquel) Pinto, X. (Xavier) Ros, E. (Emilio) Marti-del-Moral, A. (Amelia) Coltell, O. (Oscar) Ordovas, J.M. (Jose Maria) Estruch, R. (Ramón) Body mass index FTO MC4R Obesity Physical activity 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. 2014-03-17T16:41:58Z 2014-03-17T16:41:58Z 2012 info:eu-repo/semantics/article https://hdl.handle.net/10171/35531 eng info:eu-repo/semantics/openAccess info:eu-repo/semantics/openAccess application/pdf Public Library of Science
spellingShingle Body mass index
FTO
MC4R
Obesity
Physical activity
Corella, D. (Dolores)
Ortega-Azorin, C. (Carolina)
Sorli, J.V. (Jose V.)
Covas, M.I. (María Isabel)
Carrasco, P. (Paula)
Salas-Salvado, J. (Jordi)
Martinez-Gonzalez, M.A. (Miguel Ángel)
Aros, F. (Fernando)
Lapetra, J. (José)
Serra-Majem, L. (Luis)
Lamuela-Raventos, R.M. (Rosa Maria)
Gomez-Gracia, E. (Enrique)
Fiol, M. (Miquel)
Pinto, X. (Xavier)
Ros, E. (Emilio)
Marti-del-Moral, A. (Amelia)
Coltell, O. (Oscar)
Ordovas, J.M. (Jose Maria)
Estruch, R. (Ramón)
Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption
title Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption
title_full Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption
title_fullStr Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption
title_full_unstemmed Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption
title_short Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption
title_sort statistical and biological gene-lifestyle interactions of mc4r and fto with diet and physical activity on obesity: new effects on alcohol consumption
topic Body mass index
FTO
MC4R
Obesity
Physical activity
url https://hdl.handle.net/10171/35531
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