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Abstract：
To date, there has been great progress in understanding the genetic basis of ischemic stroke (IS); however, several aspects of the condition remain underexplored, including the influence of genetic factors on post-stroke outcomes and the identification of causative loci. We proposed that an analysis of the results obtained from animal models of brain ischemia could be helpful. To this end, we developed a bioinformatic approach for exploring single-nucleotide polymorphisms (SNPs) in human orthologs of rat genes expressed differentially after induced brain ischemia. Using this approach, we identified and analyzed 11 SNPs from 6 genes in 553 Russian individuals (331 patients with IS and 222 controls). We assessed the association of SNPs with the risk of IS and IS outcomes. We found that the SNPs rs858239 (GPNMB), rs907611 (LSP1), and rs494356 (TAGLN) were associated with different parameters of IS functional outcomes. In addition, the SNP rs1261025 (PDPN) was associated significantly with IS itself (p = 0.0188, recessive model). All these associations were demonstrated for the first time. Analysis of the literature suggests that they should be characterized as being inflammation related. This supports the pivotal role of inflammation in both the incidence of stroke and post-stroke outcomes. We believe the findings reported here will help with stroke prognosis in the future.
摘要：
迄今为止,在了解缺血性卒中(IS)的遗传基础方面取得了很大进展；然而，这种情况的几个方面仍未得到充分开发，包括遗传因素对卒中后结局的影响和致病基因位点的鉴定。我们建议对从脑缺血动物模型获得的结果进行分析可能会有所帮助。为此,我们开发了一种生物信息学方法，用于探索诱导脑缺血后差异表达的大鼠基因的人类直向同源物中单核苷酸多态性（SNP）。使用这种方法，我们从553名俄罗斯人(331例IS患者和222例对照)的6个基因中鉴定并分析了11个SNP.我们评估了SNP与IS和IS结局风险的关联。我们发现SNPsrs858239(GPNMB)，rs907611(LSP1),和rs494356(TAGLN)与IS功能结局的不同参数相关。此外,SNPrs1261025（PDPN）与IS本身显着相关（p=0.0188，隐性模型）。所有这些关联都是第一次被证明。文献分析表明，它们应被表征为与炎症相关。这支持了炎症在中风发生率和中风后结局中的关键作用。我们相信这里报道的发现将有助于未来的中风预后。
