TTC7B emerges as a novel risk factor for ischemic stroke through the convergence of several genome-wide approaches
TTC7B emerges as a novel risk factor for ischemic stroke through the convergence of several genome-wide approaches
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DOI：
10.1038/jcbfm.2012.24
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发表时间：
2012-06-01
影响因子：
6.3
通讯作者：
Oliveira, Sofia A.
中科院分区：
文献类型：
--
作者：
Krug, Tiago;Gabriel, Joao Paulo;Oliveira, Sofia A.
我们在此提出了一种新的方法来识别缺血性卒中（IS）易感基因，该方法涉及从几个无偏倚的遗传和基因组工具中收集数据。我们测试了IS与病例和对照组之间差异表达的基因之间的关联，然后确定哪些数据映射到先前报道的连锁峰，并在已发表的全基因组关联研究中名义上与卒中相关。我们首先对20例IS患者和20例对照组的外周血单个核细胞进行了基因表达谱分析。16个差异表达基因映射到已报道的全基因组连锁峰，包括与主要心血管疾病相关的TTC7B基因。在TTC7B位点，在565例葡萄牙IS病例和520例对照中检测了46个标记多态性的相关性。然后在570例西班牙病例和390例对照中检查了至少在一项测试中名义上相关并定义相关单倍型的标记。在西班牙和联合数据集中，TTC7B内含子5和内含子6区域的几种多态性和单倍型也与IS风险相关。因此，多个独立的证据线支持TTC7B在卒中易感性中的作用，但需要进一步的工作来确定确切的风险变异及其致病潜力。脑血流与代谢杂志（2012）32,1061-1072；doi: 10.1038 / jcbfm.2012.24;2012年3月28日在线发布
We hereby propose a novel approach to the identification of ischemic stroke (IS) susceptibility genes that involves converging data from several unbiased genetic and genomic tools. We tested the association between IS and genes differentially expressed between cases and controls, then determined which data mapped to previously reported linkage peaks and were nominally associated with stroke in published genome-wide association studies. We first performed gene expression profiling in peripheral blood mononuclear cells of 20 IS cases and 20 controls. Sixteen differentially expressed genes mapped to reported whole-genome linkage peaks, including the TTC7B gene, which has been associated with major cardiovascular disease. At the TTC7B locus, 46 tagging polymorphisms were tested for association in 565 Portuguese IS cases and 520 controls. Markers nominally associated in at least one test and defining associated haplotypes were then examined in 570 IS Spanish cases and 390 controls. Several polymorphisms and haplotypes in the intron 5 intron 6 region of TTC7B were also associated with IS risk in the Spanish and combined data sets. Multiple independent lines of evidence therefore support the role of TTC7B in stroke susceptibility, but further work is warranted to identify the exact risk variant and its pathogenic potential. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1061-1072; doi:10.1038/jcbfm.2012.24; published online 28 March 2012