Koltsova E A, Petrova E A, Khrunin A V, Khvorykh G V, Limborska S A
Pirogov Russian National Research Medical University, Moscow, Russia.
Kurchatov Institute of Molecular Genetics of National Research Center «Kurchatov Institute», Moscow, Russia.
Zh Nevrol Psikhiatr Im S S Korsakova. 2023;123(3. Vyp. 2):33-40. doi: 10.17116/jnevro202312303233.
To study the associations of nine genetic variants with the risk and dynamics of recovery (outcome) of ischemic stroke (IS) using the developed protocol for the search for genomic markers based on a bioinformatic approach to the study of single nucleotide polymorphisms (SNPs) in human orthologues of rat genes differentially expressed under conditions of induced cerebral ischemia.
We identified and analyzed nine SNPs in 553 Russians (331 IS patients and 222 controls). The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity. Functional recovery after stroke was assessed using the modified Rankin scale (mRS). The principles of selection of polymorphic markers analyzed in the study were determined according to the protocol developed by us earlier. Selected SNP tags were genotyped using real-time polymerase chain reaction (PCR) TaqMan.
The relationship of SNP with both the risk of IS and the dynamics of its recovery was investigated. SNP rs66782529 was associated with negative IS outcomes (=0.048). SNPs rs62278647 and rs2316710 were significantly associated with IS risk (=0.000029 and =0.0025, respectively). The associations for rs62278647 and rs2316710 were found only in females, suggesting a gender-related polymorphism.
This study not only reveals some new genetic links to IS and its consequences, but also shows how the study of gene variations in a rat model of cerebral ischemia can be useful in the search for genetic markers of this disease in humans.
采用基于生物信息学方法研究大鼠基因在诱导性脑缺血条件下差异表达的人类直系同源基因中的单核苷酸多态性（SNP）所开发的基因组标记搜索方案，研究9种基因变异与缺血性卒中（IS）风险及恢复（结局）动态变化之间的关联。
我们在553名俄罗斯人（331例IS患者和222名对照）中鉴定并分析了9个SNP。使用美国国立卫生研究院卒中量表（NIHSS）评估卒中严重程度。采用改良Rankin量表（mRS）评估卒中后的功能恢复情况。本研究中分析的多态性标记的选择原则是根据我们之前制定的方案确定的。使用实时聚合酶链反应（PCR）TaqMan对选定的SNP标签进行基因分型。
研究了SNP与IS风险及其恢复动态之间的关系。SNP rs66782529与IS不良结局相关（=0.048）。SNP rs62278647和rs2316710与IS风险显著相关（分别为=0.000029和=0.0025）。rs62278647和rs2316710的关联仅在女性中发现，提示存在与性别相关的多态性。
本研究不仅揭示了一些与IS及其后果相关的新的遗传联系，还展示了在脑缺血大鼠模型中研究基因变异如何有助于寻找人类该疾病的遗传标记。
