FTO Genotype, Physical Activity, and Coronary Heart Disease Risk in Swedish Men and Women
FTO Genotype, Physical Activity, and Coronary Heart Disease Risk in Swedish Men and Women
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DOI：
10.1161/circgenetics.111.000007
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发表时间：
2014-04-01
影响因子：
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通讯作者：
Nyberg, Fredrik
中科院分区：
文献类型：
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作者：
Gustavsson, Jaana;Mehlig, Kirsten;Nyberg, Fredrik
背景——易患肥胖和糖尿病的脂肪量和肥胖相关基因 (FTO) 的变异也与心血管疾病有关。有人建议体力活动可以减弱 FTO 对肥胖的影响，但尚不清楚这是否也适用于心血管疾病。因此，我们探讨了体力活动是否会改变 FTO 与冠心病 (CHD) 的关联。方法和结果 - 在 2 项瑞典人群病例对照研究中对 FTO rs9939609 (T > A) 多态性进行了基因分型，研究涉及 1743 名 CHD 病例和 4402 名对照人群（25-74 岁；41% 为女性）。通过问卷调查的方式评估闲暇时间体力活动，并定义3个级别：低、中、高。总体而言，根据年龄、性别、研究情况和体重指数进行调整后，FTO A 等位基因携带者患 CHD 的风险增加（优势比为 1.20；95% 置信区间为 1.06-1.37）。虽然与TT基因型和高活动量的A等位基因携带者相比，低体力活动的A等位基因携带者具有最高的CHD风险（比值比，3.30；95%置信区间，2.44-4.46），但FTO基因型和体力活动对CHD风险的影响近似相加，表明不存在相加相互作用。在低、中和高体力活动受试者中，A 等位基因导致 CHD 的分层特定相对风险分别为 1.11（95% 置信区间，0.77-1.60）、1.22（1.04-1.44）和 1.38（1.06-1.80），但建议的乘法交互作用并不显着。 结论-FTO rs9939609 A 等位基因携带者的 CHD 风险增加，并且这种关联不会因体力活动的增加而抵消。
Background-Variants in the fat mass- and obesity-associated gene (FTO) predisposing to obesity and diabetes mellitus have also been associated with cardiovascular disease. Physical activity has been suggested to attenuate the FTO effect on obesity, but it is unknown whether this is also true for cardiovascular disease. Therefore, we explored whether physical activity modifies the FTO association with coronary heart disease (CHD).Methods and Results-FTO rs9939609 (T > A) polymorphism was genotyped in 2 Swedish population-based case-control studies with 1743 CHD cases and 4402 population controls (25-74 years of age; 41% women). Leisure time physical activity was assessed by questionnaires, and 3 levels were defined: low, medium, and high. Overall, carriers of the FTO A allele had an increased risk of CHD (odds ratio, 1.20; 95% confidence interval, 1.06-1.37) adjusted for age, sex, study, and body mass index. Although A-allele carriers with low physical activity had the highest CHD risk (odds ratio, 3.30; 95% confidence interval, 2.44-4.46) compared with those with TT genotype and high activity, the effects of FTO genotype and physical activity on CHD risk were approximately additive, indicating the absence of additive interaction. The stratum-specific relative risks of CHD from the A allele in subjects with low, medium, and high physical activity were odds ratio 1.11 (95% confidence interval, 0.77-1.60), 1.22 (1.04-1.44), and 1.38 (1.06-1.80), respectively, but the suggested multiplicative interaction was not significant.Conclusions-FTO rs9939609 A-allele carriers have an increased CHD risk, and the association is not counteracted by increased physical activity.