Moskau Susanna, Golla Astrid, Grothe Christoph, Boes Monika, Pohl Christoph, Klockgether Thomas
Department of Neurology, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
Stroke. 2005 Jan;36(1):5-8. doi: 10.1161/01.STR.0000149936.33498.83. Epub 2004 Nov 29.
Ultrasound examination of the carotid arteries yields several quantitative measures that may serve as intermediate phenotypes in genetic studies. This study was undertaken to compare the heritabilities of 3 ultrasound measures: intima-media thickness (IMT), plaque score, and maximal stenosis.
We studied 565 individuals from 154 families ascertained by an affected parent with carotid artery atherosclerosis. IMT, plaque score, and maximal stenosis of the carotid arteries were examined by B-mode ultrasound and analyzed quantitatively. Heritability estimates were obtained by variance component analysis as implemented in the program SOLAR (sequential oligogenic linkage analysis routines). Covariates were age, sex, weight, height, body mass index (BMI), arterial hypertension, diabetes mellitus, amount of nicotine consumed, and plasma levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, LDL/HDL ratio, lipoprotein(a) [Lp(a)], triglycerides, factor VIII, factor XIII, fibrinogen, and von Willebrand factor (vWF).
After accounting for the covariables age, sex, hypertension, diabetes mellitus, and Lp(a), heritability of IMT was estimated as h2=0.61+/-0.17 (P=0.001). Variation of plaque score was influenced by age, sex, hypertension, diabetes mellitus, hypercholesterolemia, amount of nicotine consumed, factor VIII, and vWF. When these were considered, no significant heritability could be detected. Heritability of stenosis was estimated as h2=0.47+/-0.07 (P=0.006), with age, sex, BMI, hypertension, diabetes mellitus, amount of nicotine consumed, and LDL/HDL ratio as covariates.
Among the 3 ultrasound measures studied, IMT had the highest heritability. IMT was strongly influenced by genetic determinants other than those influencing known risk factors. This makes IMT a promising candidate for use as an intermediate phenotype in genetic studies aiming to identify novel genes for atherosclerosis.
颈动脉超声检查可得出多种定量指标，这些指标可作为基因研究中的中间表型。本研究旨在比较3种超声测量指标的遗传度：内膜中层厚度（IMT）、斑块评分和最大狭窄程度。
我们研究了154个家庭中的565名个体，这些家庭由患有颈动脉粥样硬化的患病父母确定。通过B型超声检查颈动脉的IMT、斑块评分和最大狭窄程度，并进行定量分析。遗传度估计通过SOLAR（顺序寡基因连锁分析程序）中实施的方差成分分析获得。协变量包括年龄、性别、体重、身高、体重指数（BMI）、动脉高血压、糖尿病、尼古丁摄入量以及血浆低密度脂蛋白（LDL）和高密度脂蛋白（HDL）胆固醇水平、LDL/HDL比值、脂蛋白(a)[Lp(a)]、甘油三酯、凝血因子VIII、凝血因子XIII、纤维蛋白原和血管性血友病因子（vWF）。
在考虑年龄、性别、高血压、糖尿病和Lp(a)等协变量后，IMT的遗传度估计为h2=0.61±0.17（P=0.001）。斑块评分的变化受年龄、性别、高血压、糖尿病、高胆固醇血症、尼古丁摄入量、凝血因子VIII和vWF的影响。考虑这些因素后，未检测到显著的遗传度。狭窄程度的遗传度估计为h2=0.47±0.07（P=0.006），协变量为年龄、性别、BMI、高血压、糖尿病、尼古丁摄入量和LDL/HDL比值。
在所研究的3种超声测量指标中，IMT的遗传度最高。IMT受影响已知危险因素之外的遗传决定因素的强烈影响。这使得IMT成为在旨在识别动脉粥样硬化新基因的基因研究中用作中间表型的有前景的候选指标。
