Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Am Heart J. 2010 Dec;160(6):1163-9. doi: 10.1016/j.ahj.2010.08.002.
Variation in the Fat-Mass and Obesity-Associated (FTO) gene has been associated with obesity, diabetes, and hypertension. However, its association with cardiovascular disease (CVD) in healthy populations and any interaction with physical activity remain unclear.
The FTO rs8050136 allele was determined in a prospective cohort study of 21,674 apparently healthy White US women in the Women's Genome Health Study.
During a mean follow-up of 12.7±2.0 years, 664 incident CVD events occurred. The risk allele (A) was associated with higher prevalence of hypertension, diabetes, and metabolic syndrome (all P<.05). In a multivariate model, there was significant association of the risk allele with CVD (hazard ratio [HR] per allele copy 1.14, 95% CI 1.01-1.28) that was no longer significant after additional adjustment for body mass index (BMI) (HR 1.10, 95% CI 0.97-1.23). There was statistical evidence of an interaction between FTO and physical activity (P=.048). We found a significant association of FTO with CVD only among less-active (≤8.8 metabolic equivalent-h/wk) women (HR 1.19, 95% CI 1.02-1.38) in multivariate analyses that included BMI. More-active women did not have this increased risk (HR 0.96, 95% CI 0.79-1.16]). In a model that adjusted for BMI, less-active/high-risk (A/A) women were at 54% increased risk of developing CVD (HR 1.54, 95% CI 1.13-2.11), compared to more-active/low-risk (C/C) women.
Carriers of the FTO risk allele have an increased risk of CVD mediated by BMI. There appears to be an interaction with physical activity, such that this risk increase is only in less-active women.
脂肪量和肥胖相关基因（FTO）的变异与肥胖、糖尿病和高血压有关。然而，它与健康人群中心血管疾病（CVD）的关系以及与体力活动的任何相互作用仍不清楚。
在妇女基因组健康研究中，对 21674 名美国白人女性进行了一项前瞻性队列研究，确定了 FTO rs8050136 等位基因。
在平均 12.7±2.0 年的随访期间，发生了 664 例 CVD 事件。风险等位基因（A）与高血压、糖尿病和代谢综合征的患病率较高有关（均 P<.05）。在多变量模型中，风险等位基因与 CVD 有显著相关性（每等位基因 1.14 的风险比[HR]，95%CI 1.01-1.28），但在进一步调整体重指数（BMI）后，这种相关性不再显著（HR 1.10，95%CI 0.97-1.23）。FTO 与体力活动之间存在统计学意义上的交互作用（P=.048）。我们发现，只有在体力活动较少（≤8.8 代谢当量-h/wk）的女性中，FTO 与 CVD 之间存在显著相关性（多变量分析中 HR 1.19，95%CI 1.02-1.38），且包含 BMI。体力活动较多的女性没有这种增加的风险（HR 0.96，95%CI 0.79-1.16]）。在调整 BMI 的模型中，体力活动较少/风险较高（A/A）的女性发生 CVD 的风险增加 54%（HR 1.54，95%CI 1.13-2.11），而体力活动较多/风险较低（C/C）的女性则没有增加。
FTO 风险等位基因的携带者发生 CVD 的风险增加，这种风险增加与 BMI 有关。似乎与体力活动存在相互作用，只有在体力活动较少的女性中才会出现这种风险增加。
