Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Diabetes Care. 2011 Mar;34(3):675-80. doi: 10.2337/dc10-0948. Epub 2011 Jan 25.
Variation in the fat mass and obesity-associated (FTO) gene is associated with obesity. The extent to which separate and combined effects of physical activity and caloric intake modify this association remains unclear.
FTO polymorphism rs8050136 was measured, and physical activity, caloric intake, and anthropometrics were self-reported in 21,675 apparently healthy Caucasian women.
The effect of the risk allele (A) on BMI was larger among inactive or higher intake women, with additive effects of inactivity and high intake on the associated genetic risk. Specifically, each A allele was associated with mean BMI difference of +0.73 (SE 0.08) kg/m(2) among inactive women (≤ median, 8.8 MET-hours/week), compared with +0.31 (0.06) kg/m(2), P < 0.0001, among active women (>8.8 MET-hours/week). Similarly, each A allele was associated with mean BMI difference of +0.65 (0.07) among high intake women (>median, 1,679 kcals/day), compared with +0.38 (0.07) kg/m(2), P = 0.005, among low intake women (≤ 1,679 kcals/day). Among inactive/high intake women, each A allele was associated with mean BMI difference of +0.97 (0.11) kg/m(2) vs. +0.22 (0.08) kg/m(2) among inactive/low intake women, P < 0.0001. Among inactive/high intake women, each A allele carried increased risk of obesity (odds ratio 1.39, 95% CI 1.27-1.52) and diabetes (odds ratio 1.36, 95% CI 1.07-1.73).
In this study, lifestyle factors modified the genetic risk of FTO on obesity phenotypes, particularly among women who were both inactive and had high intake. Healthier lifestyle patterns blunted but did not completely eliminate the associated genetic risk.
脂肪量和肥胖相关基因（FTO）的变异与肥胖有关。运动和热量摄入的单独和综合作用在多大程度上改变这种关联尚不清楚。
在 21675 名看似健康的白种女性中，测量了 FTO 多态性 rs8050136，报告了身体活动、热量摄入和人体测量数据。
在不活跃或高摄入的女性中，风险等位基因（A）对 BMI 的影响更大，不活跃和高摄入对相关遗传风险有累加作用。具体来说，在不活跃的女性（≤中位数，每周 8.8 代谢当量小时）中，每个 A 等位基因与平均 BMI 差异为+0.73（0.08）kg/m²，而在活跃的女性（>8.8 代谢当量小时/周）中为+0.31（0.06）kg/m²，P<0.0001。同样，在高摄入的女性（>中位数，每天 1679 卡路里）中，每个 A 等位基因与平均 BMI 差异为+0.65（0.07）kg/m²，而在低摄入的女性（≤每天 1679 卡路里）中为+0.38（0.07）kg/m²，P=0.005。在不活跃/高摄入的女性中，每个 A 等位基因与平均 BMI 差异为+0.97（0.11）kg/m²相比，在不活跃/低摄入的女性中为+0.22（0.08）kg/m²，P<0.0001。在不活跃/高摄入的女性中，每个 A 等位基因都增加了肥胖的风险（比值比 1.39，95%置信区间 1.27-1.52）和糖尿病（比值比 1.36，95%置信区间 1.07-1.73）。
在这项研究中，生活方式因素改变了 FTO 对肥胖表型的遗传风险，尤其是在那些既不活跃又摄入高热量的女性中。更健康的生活方式模式减弱了但并没有完全消除相关的遗传风险。
