National Research Centre "Kurchatov Institute", Kurchatov Sq. 2, Moscow 123182, Russia.
Faculty of Biotechnology and Industrial Ecology, Mendeleev University of Chemical Technology of Russia, Miusskaya Sq. 9, Moscow 125047, Russia.
Int J Mol Sci. 2023 Apr 6;24(7):6831. doi: 10.3390/ijms24076831.
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 (), rs907611 (), and rs494356 () were associated with different parameters of IS functional outcomes. In addition, the SNP rs1261025 () was associated significantly with IS itself ( = 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.
迄今为止,人们在理解缺血性中风(IS)的遗传基础方面已经取得了重大进展;然而,该病症的几个方面仍未得到充分探索,包括遗传因素对中风后结果的影响以及致病基因座的确定。我们提出,分析脑缺血动物模型的结果可能会有所帮助。为此,我们开发了一种生物信息学方法,用于探索在诱导脑缺血后表达差异的大鼠基因的人类同源物中的单核苷酸多态性(SNPs)。使用这种方法,我们从 553 名俄罗斯个体(331 名 IS 患者和 222 名对照)的 6 个基因中鉴定和分析了 11 个 SNP。我们评估了 SNP 与 IS 风险和 IS 结果的关联。我们发现 SNP rs858239()、rs907611()和 rs494356()与 IS 功能结果的不同参数相关。此外,SNP rs1261025()与 IS 本身显著相关(= 0.0188,隐性模型)。所有这些关联均为首次发现。对文献的分析表明,它们与炎症有关。这支持了炎症在中风发生和中风后结果中的关键作用。我们相信,这里报告的发现将有助于未来的中风预后。