Fox Caroline S, Polak Joseph F, Chazaro Irmarie, Cupples Adrienne, Wolf Philip A, D'Agostino Ralph A, O'Donnell Christopher J
National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Mass 01702, USA.
Stroke. 2003 Feb;34(2):397-401. doi: 10.1161/01.str.0000048214.56981.6f.
Carotid intima-media thickness (IMT) is a quantitative measure of subclinical atherosclerosis that is predictive of subsequent myocardial infarction and stroke. There is controversy regarding the proportion of variability in IMT explained by genetic factors. Thus, it is uncertain whether carotid IMT is a heritable trait that can be used in genetic studies.
From 1996 to 1998, we measured carotid IMT in 906 men (mean age, 56.7 years) and 980 women (mean age, 57.4 years) from 586 extended families (1630 sib pairs) in the Framingham Offspring cohort. B-mode carotid ultrasonography was used to define mean and maximum IMT of the common carotid artery (CCA) and internal carotid artery (ICA). Correlation coefficients were calculated in pairs of siblings. Variance component methods were used to estimate heritability with crude, age- and sex-adjusted, and multivariable-adjusted normalized deviates.
Multivariable-adjusted correlation coefficients for mean CCA and ICA IMT were 0.16 and 0.16, respectively. Crude, age- and sex-adjusted, and multivariable-adjusted heritabilities were 0.67, 0.44, and 0.38 for the mean CCA IMT (all P<0.001) and 0.43, 0.37, and 0.35 for the mean ICA IMT (all P<0.001). For CCA IMT, 27% of the overall variance was due to measured covariates; 38% was due to heritable factors.
These data suggest that a substantial proportion of the variability in carotid IMT is explained by genetic factors. Further studies of genetic linkage and candidate gene association are warranted to identify specific genetic variants predisposing to subclinical atherosclerosis and stroke.
颈动脉内膜中层厚度（IMT）是亚临床动脉粥样硬化的一种定量测量指标，可预测随后发生的心肌梗死和中风。关于遗传因素在IMT变异性中所占比例存在争议。因此，颈动脉IMT是否为可用于基因研究的遗传性状尚不确定。
1996年至1998年，我们在弗雷明汉后代队列中对来自586个大家庭（1630对同胞对）的906名男性（平均年龄56.7岁）和980名女性（平均年龄57.4岁）测量了颈动脉IMT。采用B型颈动脉超声检查来确定颈总动脉（CCA）和颈内动脉（ICA）的平均和最大IMT。计算同胞对之间的相关系数。采用方差成分法，用原始、年龄和性别调整以及多变量调整的标准化偏差来估计遗传力。
平均CCA和ICA IMT的多变量调整相关系数分别为0.16和0.16。平均CCA IMT的原始、年龄和性别调整以及多变量调整遗传力分别为0.67、0.44和0.38（均P<0.001），平均ICA IMT的分别为0.43、0.37和0.35（均P<0.001）。对于CCA IMT，总体方差的27%归因于测量的协变量；38%归因于遗传因素。
这些数据表明，颈动脉IMT变异性的很大一部分可由遗传因素解释。有必要进一步开展基因连锁和候选基因关联研究，以确定易患亚临床动脉粥样硬化和中风的特定基因变异。
