Statistical and biological gene-lifestyle interactions of MC4R and FTO with Diet and physical activity on obesity: new effects on alcohol consumption
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comunitat-uji-handle2:10234/7038
comunitat-uji-handle3:10234/8634
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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 consumptionAuthor (s)
Date
2012Publisher
Public Library of ScienceISSN
1932-6203Type
info:eu-repo/semantics/articlePublisher version
http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjou ...Version
info:eu-repo/semantics/publishedVersionAbstract
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 ... [+]
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 bodymass 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 (nonstatistical)
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+/2SE: 20.57+/20.16 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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PLoS ONE, December, Volume 7, Issue 12, e52344Rights
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Except where otherwise noted, this item's license is described as © 2012 Corella et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.