Gustavsson Jaana, Mehlig Kirsten, Leander Karin, Lissner Lauren, Björck Lena, Rosengren Annika, Nyberg Fredrik
Occupational and Environmental Medicine.
Circ Cardiovasc Genet. 2014 Apr;7(2):171-7. doi: 10.1161/CIRCGENETICS.111.000007. Epub 2014 Mar 12.
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).
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.
FTO rs9939609 A-allele carriers have an increased CHD risk, and the association is not counteracted by increased physical activity.
肥胖和糖尿病相关基因（FTO）中的变异与心血管疾病有关，这些变异易导致肥胖。有研究表明体育活动可减弱FTO对肥胖的影响，但对于心血管疾病是否如此尚不清楚。因此，我们探讨了体育活动是否会改变FTO与冠心病（CHD）之间的关联。
在两项基于瑞典人群的病例对照研究中，对1743例冠心病患者和4402名人群对照（年龄25 - 74岁；41%为女性）进行了FTO rs9939609（T>A）多态性基因分型。通过问卷调查评估休闲时间的体育活动情况，并定义了三个水平：低、中、高。总体而言，在对年龄、性别、研究和体重指数进行调整后，FTO A等位基因携带者患冠心病的风险增加（比值比，1.20；95%置信区间，1.06 - 1.37）。尽管与TT基因型且体育活动水平高的人相比，体育活动水平低的A等位基因携带者患冠心病的风险最高（比值比，3.30；95%置信区间，2.44 - 4.46），但FTO基因型和体育活动对冠心病风险的影响大致呈相加关系，表明不存在相加相互作用。体育活动水平低、中、高的受试者中，A等位基因导致冠心病的分层特异性相对风险分别为比值比1.11（95%置信区间，0.77 - 1.60）、1.22（1.04 - 1.44）和1.38（1.06 - 1.80），但所提示的相乘相互作用并不显著。
FTO rs9939609 A等位基因携带者患冠心病风险增加，且这种关联不会因体育活动增加而被抵消。
