Association between variations in coagulation system genes and carotid plaque.
Association between variations in coagulation system genes and carotid plaque.
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DOI：
10.1016/j.jns.2012.08.020
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发表时间：
2012-12-15
影响因子：
4.4
通讯作者：
Rundek, Tatjana
中科院分区：
文献类型：
--
作者：
Della-Morte, David;Beecham, Ashley;Dong, Chuanhui;Wang, Liyong;McClendon, Mark S.;Gardener, Hannah;Blanton, Susan H.;Sacco, Ralph L.;Rundek, Tatjana
关键词：
凝血和纤溶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参与凝血系统的基因之间的关系的数据很少。本研究的目的是检测凝血系统基因的单核苷酸多态(SNPs)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的遗传决定因素研究中，287名多米尼加人通过高分辨率B型颈动脉超声检查了颈动脉斑块的存在、厚度和表面不规则性。在控制年龄、性别、吸烟、高血压、血脂异常和糖尿病的情况下，采用Logistic回归检验23个凝血系统基因中的101个SNPs与斑块表型的相关性。在基因内检测了单倍型和基因间的相互作用。在301名多米尼加人的独立样本中进行了中到高度(R2>；0.25)连锁不平衡(LD)与发现分析(p≤0.01)中的SNPs的随访。在两组数据中，颈动脉斑块的患病率(47%发现；46%随访)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≤0.0 1)。在随访中，vWF中的5个SNP与斑块大小相关(p≤0.05)。SERPINE1是单倍型和交互作用分析中的一个额外的感兴趣的基因。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。
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 (r2>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 followup, 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.
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