Qi Qibin, Downer Mary K, Kilpeläinen Tuomas O, Taal H Rob, Barton Sheila J, Ntalla Ioanna, Standl Marie, Boraska Vesna, Huikari Ville, Kiefte-de Jong Jessica C, Körner Antje, Lakka Timo A, Liu Gaifen, Magnusson Jessica, Okuda Masayuki, Raitakari Olli, Richmond Rebecca, Scott Robert A, Bailey Mark E S, Scheuermann Kathrin, Holloway John W, Inskip Hazel, Isasi Carmen R, Mossavar-Rahmani Yasmin, Jaddoe Vincent W V, Laitinen Jaana, Lindi Virpi, Melén Erik, Pitsiladis Yannis, Pitkänen Niina, Snieder Harold, Heinrich Joachim, Timpson Nicholas J, Wang Tao, Yuji Hinoda, Zeggini Eleftheria, Dedoussis George V, Kaplan Robert C, Wylie-Rosett Judith, Loos Ruth J F, Hu Frank B, Qi Lu
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY Department of Nutrition, Harvard School of Public Health, Boston, MA
Department of Nutrition, Harvard School of Public Health, Boston, MA.
Diabetes. 2015 Jul;64(7):2467-76. doi: 10.2337/db14-1629. Epub 2015 Feb 26.
The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1-18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake; and 2) the interaction between the FTO variant and dietary intake, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake (effect per allele = 14.3 kcal/day [95% CI 5.9, 22.7 kcal/day], P = 6.5 × 10(-4)), but not with protein, carbohydrate, or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele = 0.08 SD [0.03, 0.12 SD], P for interaction = 7.2 × 10(-4)): the association between FTO genotype and BMI was much stronger in individuals with high protein intake (effect per allele = 0.10 SD [0.07, 0.13 SD], P = 8.2 × 10(-10)) than in those with low intake (effect per allele = 0.04 SD [0.01, 0.07 SD], P = 0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake, and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents.
FTO基因存在对肥胖及肥胖风险影响最为显著的变异。既往数据支持FTO变异在影响食物摄入量方面发挥作用。我们对来自14项研究的16094名1至18岁的男孩和女孩进行了综合分析，以检验以下内容：1）FTO rs9939609变异（或一个替代指标）与总能量及宏量营养素摄入量之间的关联；2）FTO变异与饮食摄入量之间的相互作用及其对体重指数（BMI）的影响。我们发现，FTO变异增加BMI的等位基因（次要等位基因）与总能量摄入量增加相关（每个等位基因的效应为14.3千卡/天[95%可信区间5.9，22.7千卡/天]，P = 6.5×10⁻⁴），但与蛋白质、碳水化合物或脂肪摄入量无关。我们还发现，蛋白质摄入量改变了FTO变异与BMI之间的关联（每个等位基因的交互效应为0.08标准差[0.03，0.12标准差]，交互作用的P值 = 7.2×10⁻⁴）：在高蛋白摄入量个体中，FTO基因型与BMI之间的关联要强得多（每个等位基因的效应为0.10标准差[0.07，0.13标准差]，P = 8.2×10⁻¹⁰），而在低蛋白摄入量个体中则较弱（每个等位基因的效应为0.04标准差[0.01，0.07标准差]，P = 0.02）。我们的研究结果表明，赋予更高BMI易感性的FTO变异与更高的总能量摄入量相关，且较低的膳食蛋白质摄入量会减弱儿童和青少年中FTO基因型与肥胖之间的关联。
