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细胞黏附分子的数量遗传学分析:费尔斯纵向研究

Quantitative genetic analysis of cellular adhesion molecules: the Fels Longitudinal Study.

作者信息

Lee Miryoung, Czerwinski Stefan A, Choh Audrey C, Demerath Ellen W, Sun Shumei S, Chumlea Wm C, Towne Bradford, Siervogel Roger M

机构信息

Lifespan Health Research Center, Department of Community Health, Wright State University, School of Medicine, 3171 Research Blvd., Dayton, OH 45420, USA.

出版信息

Atherosclerosis. 2006 Mar;185(1):150-8. doi: 10.1016/j.atherosclerosis.2005.05.027. Epub 2005 Jul 7.

Abstract

Circulating concentrations of inflammatory markers predict cardiovascular disease (CVD) risk and are closely associated with obesity. However, little is known concerning genetic influences on serum levels of inflammatory markers. In this study, we estimated the heritability (h2) of soluble cellular adhesion molecule (sCAM) concentrations and examined the correlational architecture between different sCAMs. The study population included 234 men and 270 women aged 18-76 years, belonging to 121 families participating in the Fels Longitudinal Study. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sESEL-1) and P-selectin (sPSEL-1) were assayed using commercially available kits. A variance components-based maximum likelihood method was used to estimate the h2 of the different serum inflammatory markers while simultaneously adjusting for the effects of known CVD risk factors, such as age and smoking. Additionally, we used bivariate extensions of these methods to estimate genetic and random environmental correlations among sCAMs. Levels of sCAMs were significantly heritable: h2=0.24+/-0.10 for sICAM-1, h2=0.22+/-0.10 for sVCAM-1, h2=0.50+/-0.11 for sESEL-1, and h2=0.46+/-0.10 for sPSEL-1. In addition, a significant genetic correlation (rho(G)=0.63) was found between sICAM-1 and sVCAM-1 indicating some degree of shared genetic control. In the Fels Longitudinal Study, the levels of four sCAMs are significantly influenced by genetic effects, and sICAM-1 shares a common genetic background with sVCAM-1.

摘要

炎症标志物的循环浓度可预测心血管疾病(CVD)风险,且与肥胖密切相关。然而,关于基因对炎症标志物血清水平的影响却知之甚少。在本研究中,我们估计了可溶性细胞黏附分子(sCAM)浓度的遗传力(h2),并研究了不同sCAM之间的相关结构。研究人群包括234名男性和270名女性,年龄在18至76岁之间,来自参与费尔斯纵向研究的121个家庭。使用市售试剂盒检测可溶性细胞间黏附分子-1(sICAM-1)、血管细胞黏附分子-1(sVCAM-1)、E-选择素(sESEL-1)和P-选择素(sPSEL-1)的血清水平。采用基于方差成分的最大似然法估计不同血清炎症标志物的h2,同时调整年龄和吸烟等已知CVD危险因素的影响。此外,我们使用这些方法的双变量扩展来估计sCAM之间的遗传和随机环境相关性。sCAM水平具有显著的遗传性:sICAM-1的h2 = 0.24 ± 0.10,sVCAM-1的h2 = 总述0.22 ± 0.10,sESEL-1的h2 = 0.50 ± 0.11,sPSEL-1的h2 = 0.46 ± 0.10。此外,sICAM-1和sVCAM-1之间存在显著的遗传相关性(rho(G)=0.63),表明存在一定程度的共同遗传控制。在费尔斯纵向研究中,四种sCAM的水平受到遗传效应的显著影响,且sICAM-1与sVCAM-1具有共同的遗传背景。

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