Heritability of carotid artery atherosclerotic lesions - An ultrasound study in 154 families
Heritability of carotid artery atherosclerotic lesions - An ultrasound study in 154 families
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DOI：
10.1161/01.str.0000149936.33498.83
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发表时间：
2005-01-01
期刊：
影响因子：
8.3
通讯作者：
Klockgether, T
中科院分区：
文献类型：
--
作者：
Moskau, S;Golla, A;Klockgether, T
背景和目的--颈动脉超声检查可产生几种定量指标，可作为遗传学研究中的中间表型。本研究进行了比较的遗传性3超声测量：内膜中层厚度（IMT），斑块评分，和最大stenosis. Methods，我们研究了565个人从154个家庭确定的受影响的父母与颈动脉粥样硬化。采用B超检测颈动脉IMT、斑块积分、最大狭窄程度并进行定量分析。遗传力估计值通过在程序SOLAR（顺序寡基因连锁分析程序）中执行的方差分量分析获得。协变量为年龄、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、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）胆固醇的血浆水平、LDL/HDL比值、脂蛋白（a）[Lp（a）]、甘油三酯、因子VIII、因子XIII、纤维蛋白原和血管性血友病因子（vWF）。在性别、高血压、糖尿病和Lp（a）的影响下，IMT的遗传度为h（2）=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、因子VIII和vWF的影响。当考虑这些因素时，没有检测到显著的遗传力。狭窄的遗传度估计为h（2）=0.47+/-0.07（P=0.006），年龄、性别、BMI、高血压、糖尿病、尼古丁摄入量和LDL/HDL比值作为协变量。IMT受遗传因素的强烈影响，而不是那些影响已知的危险因素。这使得IMT成为一个有希望的候选者，可用作旨在鉴定动脉粥样硬化新基因的遗传学研究中的中间表型。
Background and Purpose-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.Methods-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).Results-After accounting for the covariables age, sex, hypertension, diabetes mellitus, and Lp( a), heritability of IMT was estimated as h(2)=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 h(2)=0.47+/-0.07 (P=0.006), with age, sex, BMI, hypertension, diabetes mellitus, amount of nicotine consumed, and LDL/HDL ratio as covariates.Conclusions-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.