Zhao J, Cheema F A, Reddy U, Bremner J D, Su S, Goldberg J, Snieder H, Vaccarino V
Department of Medicine, Division of Cardiology, Emory University School of Medicine, 1256 Briarcliff Road NE, Atlanta, GA 30306, USA.
J Thromb Haemost. 2007 Dec;5(12):2386-92. doi: 10.1111/j.1538-7836.2007.02760.x. Epub 2007 Sep 10.
Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker for early atherosclerotic vascular disease and future cardiovascular events.
To estimate the heritability of brachial artery FMD using a twin design.
We estimated the heritability of FMD using 94 middle-aged male twin pairs. FMD was measured by ultrasound, and traditional coronary heart disease risk factors were measured. Genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in FMD.
The mean age of the twin participants was 54.9 +/- 2.8 years. The mean FMD was 0.047 +/- 0.030. The intraclass correlation coefficient was higher in MZ twins [0.38, 95% confidence interval (CI) 0.32-0.43] than in DZ twins (0.19, 95% CI 0.11-0.26), suggesting a role of genetic influence in FMD variation. Structural equation modeling showed that both genetic and unique environmental factors contributed significantly to the variation in FMD. The crude FMD heritability was 0.37 (95% CI 0.15-0.54). After adjustment for traditional cardiovascular risk factors, including age, total cholesterol, blood pressure, and body mass index, the heritability of FMD was 39% (95% CI 0.18-0.56). The remaining variation in FMD could be explained by individual-specific environment.
This is the first study using twins to estimate the relative contributions of genetics and environment to the variation in FMD in a US population. Our results demonstrate a moderate genetic effect on brachial artery FMD, independent of traditional coronary risk factors. Our data also highlight the importance of unique environment on the variability in FMD.
通过肱动脉血流介导的血管舒张功能(FMD)评估的内皮功能障碍是早期动脉粥样硬化性血管疾病和未来心血管事件的一个标志物。
采用双生子设计评估肱动脉FMD的遗传度。
我们使用94对中年男性双生子对来评估FMD的遗传度。通过超声测量FMD,并测量传统的冠心病危险因素。采用遗传建模技术来确定基因和环境对FMD变异的相对贡献。
双生子参与者的平均年龄为54.9±2.8岁。平均FMD为0.047±0.030。同卵双生子的组内相关系数[0.38,95%置信区间(CI)0.32 - 0.43]高于异卵双生子(0.19,95%CI 0.11 - 0.26),提示遗传影响在FMD变异中起作用。结构方程模型显示,遗传因素和独特环境因素均对FMD变异有显著贡献。FMD的粗遗传度为0.37(95%CI 0.15 - 0.54)。在对包括年龄、总胆固醇、血压和体重指数等传统心血管危险因素进行校正后,FMD的遗传度为39%(95%CI 0.18 - 0.56)。FMD的其余变异可由个体特异性环境解释。
这是第一项在美国人群中使用双生子来估计基因和环境对FMD变异相对贡献的研究。我们的结果表明基因对肱动脉FMD有中度影响,且独立于传统的冠心病危险因素。我们的数据还突出了独特环境对FMD变异性的重要性。