Carotid plaque and candidate genes related to inflammation and endothelial function in Hispanics from northern Manhattan.
Carotid plaque and candidate genes related to inflammation and endothelial function in Hispanics from northern Manhattan.
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DOI：
10.1161/strokeaha.110.591065
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发表时间：
2011-04
期刊：
影响因子：
8.3
通讯作者：
Rundek T
中科院分区：
文献类型：
--
作者：
Gardener H;Beecham A;Cabral D;Yanuck D;Slifer S;Wang L;Blanton SH;Sacco RL;Juo SH;Rundek T
遗传因素对颈动脉粥样硬化斑块的影响尚不清楚。本研究探讨了颈动脉斑块与炎症和内皮功能相关基因的单核苷酸多态性（SNP）之间的关系。对来自北方曼哈顿研究的287名多米尼加人（平均年龄64±7岁，58%为女性）进行了高分辨率B型超声检查颈动脉斑块，共询问了43个涉及炎症和内皮功能的基因（197个SNP）。使用加性遗传模型，进行多元逻辑回归分析，进行基因内单倍型分析，并检查基因之间的相互作用。结果进行了验证，在一个独立的301多米尼加人。143例（47%）参与者存在颈动脉斑块。9个基因具有至少一个与颈动脉斑块表型相关的SNP（p≤0.01）：TNF、NOS2A、IL6R、TNFSF 4、PPARA、IL1A、TLR 4、ITGA 2、HABP 2。在验证分析中，TNFSF 4、PPARA、TLR 4、ITGA 2和HABP2中的SNP也与相同的颈动脉表型有关。单倍型分析揭示了另一个感兴趣的基因，VCAM 1。我们报告了多米尼加样本中涉及炎症和内皮功能的10个基因的变异与颈动脉斑块表型之间的新关联，并在独立的多米尼加样本中复制了5个基因。
The genetic influence on carotid atherosclerotic plaque is mostly unknown. This study examines the association between carotid plaque and single nucleotide polymorphisms (SNPs) in selected genes implicated in inflammation and endothelial function. A total of 43 genes (197 SNPs) involved in inflammation and endothelial function were interrogated in 287 Dominicans from the Northern Manhattan Study (mean age 64±7 years, 58% women) who had undergone high-resolution B-mode ultrasound for examination of carotid plaque. Using an additive genetic model, multiple logistic regression analyses were conducted, a within gene haplotype analysis was performed and interactions between genes were examined. Results were validated in an independent set of 301 Dominicans. Carotid plaque was present in 143(47%) participants. Nine genes had at least one SNP associated (p≤0.01) with carotid plaque phenotypes: TNF, NOS2A, IL6R, TNFSF4, PPARA, IL1A, TLR4, ITGA2, HABP2. SNPs in TNFSF4, PPARA, TLR4, ITGA2, and HABP2 were also implicated with the same carotid phenotype in the validation analysis. Haplotype analysis revealed an additional gene of interest, VCAM1. We report novel associations between variations in ten genes involved in inflammation and endothelial function and carotid plaque phenotypes in a Dominican sample, with replication for five genes in an independent Dominican sample.