Studies of Genetic Variants in Patients with Ischemic Stroke in Human Orthologs of Rat Genes
Neuroscience and Behavioral Physiology(2023)
摘要
Objectives . To study the associations of nine genetic variants with the risk of developing ischemic stroke (IS) and the dynamics of recovery from it using a protocol developed for seeking genomic markers based on a bioinformatics approach to the study of single nucleotide polymorphisms (SNP) in human orthologs of rat genes differentially expressed in conditions of induced cerebral ischemia. Materials and methods . We identified and analyzed nine SNP in 553 Russians (331 patients with IS 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 for selecting the polymorphic markers analyzed in the study were defined according to the protocol developed in our previous work. Selected SNP tags were genotyped using the TaqMan real-time polymerase chain reaction (PCR). Results . Associations of SNP with both the risk of developing IS and the dynamics of recovery from it were studied. SNP rs66782529 (LGALS3) was associated with unfavorable stroke outcomes ( p = 0.048). SNP rs62278647 and rs2316710 (PTX3) were significantly associated with the risk of developing IS ( p = 0.000029 and p = 0.0025, respectively). These correlations for rs62278647 and rs2316710 were found only in women, suggesting a sex-related association of the PTX3 polymorphism. Conclusions . This study not only reveals some new genetic links to IS and its consequences, but also shows how studying gene variations in a rat model of cerebral ischemia can be useful in seeking genetic markers of this disease in humans.
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关键词
single nucleotide polymorphisms,outcome of ischemic stroke,rat model,cerebral ischemia
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