Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, Valencia, Spain.
PLoS One. 2012;7(12):e52344. doi: 10.1371/journal.pone.0052344. Epub 2012 Dec 21.
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.
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.
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.
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).
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.
脂肪量和肥胖（FTO）和黑素皮质素 4 受体（MC4R）是与肥胖相关的基因。这可能是通过食物摄入，但结果是矛盾的。饮食或其他生活方式因素的调节也不太清楚。
研究 MC4R 和 FTO 与体重的关联是否受饮食和体力活动（PA）的调节，并研究它们与酒精和食物摄入的关系。
在 7052 名高心血管风险患者中，通过验证问卷评估地中海饮食（AdMedDiet）和体力活动（PA）的依从性。测定 MC4R rs17782313 和 FTO rs9939609。分析独立和联合关联（综合遗传评分）以及统计和生物学基因-生活方式相互作用。
FTO rs9939609 与更高的体重指数（BMI）、腰围（WC）和肥胖（P<0.05）相关。MC4R rs17782313 也有类似但不显著的趋势。它们的加性效应（综合评分）是显著的，我们观察到每个等位基因增加 7%的肥胖风险（OR=1.07；95%CI 1.01-1.13）。我们发现与 PA 存在相关的统计学相互作用（P<0.05）。因此，在活跃的个体中，与更高的 BMI、WC 或肥胖的关联没有被检测到。在 AdMedDiet 和 rs9939609 与综合评分之间发现了生物学（非统计学）相互作用。在携带 4 或 3 个风险等位基因的个体中，更大的 AdMedDiet 抵消了他们的遗传倾向，表现出与无风险等位基因相似的 BMI（P=0.502），而与低 AdMedDiet 的个体相比，他们的 BMI 也更低（P=0.021）。我们没有发现任何与能量或宏量营养素一致的关联，但发现这些多态性与变异等位基因携带者的低酒精摄入量之间存在新的关联（变异等位基因每评分等位基因的差异为-0.57+/-0.16 g/d；P=0.001）。
与 PA 和饮食的统计学和生物学相互作用调节了 FTO 和 MC4R 多态性对肥胖的影响。与酒精消耗的新关联似乎独立于其对 BMI 的影响。
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