Institute of Molecular Genetics of National Research Center "Kurchatov Institute", Kurchatov Sq. 2, 123182 Moscow, Russia.
Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.
Genes (Basel). 2021 Nov 30;12(12):1938. doi: 10.3390/genes12121938.
Although there has been great progress in understanding the genetic bases of ischemic stroke (IS), many of its aspects remain underexplored. These include the genetics of outcomes, as well as problems with the identification of real causative loci and their functional annotations. Therefore, analysis of the results obtained from animal models of brain ischemia could be helpful. We have developed a bioinformatic approach exploring single nucleotide polymorphisms (SNPs) in human orthologues of rat genes expressed differentially under conditions of induced brain ischemia. Using this approach, we identified and analyzed nine SNPs in 553 Russian individuals (331 patients with IS and 222 controls). We explored the association of SNPs with both IS outcomes and with the risk of IS. SNP rs66782529 () was associated with negative IS outcomes ( = 0.048). SNPs rs62278647 and rs2316710 () were associated significantly with IS ( = 0.000029 and = 0.0025, respectively). These correlations for rs62278647 and rs2316710 were found only in women, which suggests a sex-specific association of the polymorphism. Thus, this research not only reveals some new genetic associations with IS and its outcomes but also shows how exploring variations in genes from a rat model of brain ischemia can be of use in searching for human genetic markers of this disorder.
尽管在理解缺血性中风（IS）的遗传基础方面已经取得了很大进展，但仍有许多方面尚未得到充分探索。这些方面包括结局的遗传学，以及确定真正的因果基因座及其功能注释的问题。因此，分析脑缺血动物模型的结果可能会有所帮助。我们开发了一种生物信息学方法，探索了在诱导性脑缺血条件下差异表达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，我们在 553 名俄罗斯个体（331 名 IS 患者和 222 名对照）中鉴定和分析了 9 个 SNP。我们探讨了 SNP 与 IS 结局和 IS 风险的相关性。SNP rs66782529 () 与不良 IS 结局相关（ = 0.048）。SNP rs62278647 和 rs2316710 () 与 IS 显著相关（ = 0.000029 和 = 0.0025，分别）。rs62278647 和 rs2316710 的这些相关性仅在女性中发现，这表明 多态性与性别特异性相关。因此，这项研究不仅揭示了一些与 IS 及其结局新的遗传关联，还表明了从脑缺血大鼠模型中探索基因变异如何有助于寻找该疾病的人类遗传标志物。
