Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
J Neurol Sci. 2012 Dec 15;323(1-2):93-8. doi: 10.1016/j.jns.2012.08.020. Epub 2012 Sep 13.
Genetic variation in coagulation and fibrinolysis may affect the development of subclinical atherosclerosis modifying the risk of stroke and cardiovascular disease. However, data on the relationship between subclinical atherosclerosis and genes involved in the coagulation system are sparse. The objective of this study is to examine the association between single nucleotide polymorphisms (SNPs) in coagulation system genes and subclinical carotid plaque phenotypes.
From the Genetic Determinants of Subclinical Carotid Disease Study, 287 Dominicans were examined for carotid plaque presence, thickness, and surface irregularity by high-resolution B-mode carotid ultrasound. Logistic regression was used to test for association between 101 SNPs in 23 coagulation system genes and plaque phenotypes while controlling for age, sex, smoking, hypertension, dyslipidemia, and diabetes. Within gene haplotypes and interactions between genes were examined. A follow-up of SNPs in moderate to high (r(2)>0.25) linkage disequilibrium (LD) with those implicated in the discovery analysis (p ≤ 0.01) was performed in an independent sample of 301 Dominicans.
The prevalence of carotid plaque (47% discovery; 46% follow-up) as well as the mean age (65 ± 8 discovery; 65 ± 9 follow-up) of the participants was similar in both datasets. Two genes (vWF and THBS1) were associated (p ≤ 0.01) with plaque size and surface irregularity. In follow-up, 5 SNPs in vWF were associated (p ≤ 0.05) with plaque size. SERPINE1 was an additional gene of interest in the haplotype and interaction analyses.
Variation in the vWF, THBS1, and SERPINE1 gene may play an important role in the pathogenesis of atherosclerotic plaque.
凝血和纤溶系统的遗传变异可能会影响亚临床动脉粥样硬化的发展，从而改变中风和心血管疾病的风险。然而，关于亚临床动脉粥样硬化与凝血系统相关基因之间关系的数据还很匮乏。本研究旨在探讨凝血系统基因单核苷酸多态性（SNP）与亚临床颈动脉斑块表型之间的关系。
从亚临床颈动脉疾病遗传决定因素研究中，对 287 名多米尼加人进行了高分辨率 B 型超声颈动脉斑块的存在、厚度和表面不规则性检查。通过逻辑回归，在控制年龄、性别、吸烟、高血压、血脂异常和糖尿病的情况下，检测 23 个凝血系统基因中的 101 个 SNP 与斑块表型之间的关联。同时还检测了基因内单倍型和基因间的相互作用。对在发现分析中具有中度至高度（r(2)>0.25）连锁不平衡（LD）的 SNP（p≤0.01）和那些有意义的 SNP 进行了在一个由 301 名多米尼加人组成的独立样本中的随访。
两个数据集的颈动脉斑块（47%发现；46%随访）的患病率以及参与者的平均年龄（65±8 发现；65±9 随访）相似。两个基因（vWF 和 THBS1）与斑块大小和表面不规则性相关（p≤0.01）。在随访中，vWF 中的 5 个 SNP 与斑块大小相关（p≤0.05）。SERPINE1 在单倍型和相互作用分析中也是一个重要的基因。
vWF、THBS1 和 SERPINE1 基因的变异可能在动脉粥样硬化斑块的发病机制中起重要作用。
