Examination of Genetic Variants Revealed from a Rat Model of Brain Ischemia in Patients with Ischemic Stroke: A Pilot Study

Abstract

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 (LGALS3) was associated with negative IS outcomes (p = 0.048). SNPs rs62278647 and rs2316710 (PTX3) were associated significantly with IS (p = 0.000029 and p = 0.0025, respectively). These correlations for rs62278647 and rs2316710 were found only in women, which suggests a sex-specific association of the PTX3 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.

The Study of the Association of Polymorphisms in LSP1, GPNMB, PDPN, TAGLN, TSPO, and TUBB6 Genes with the Risk and Outcome of Ischemic Stroke in the Russian Population

“…The patients with low scores are then compared to those with high scores [ 7 , 20 ]. Because there is no consensus regarding optimal grouping, we also applied directional ∆mRS, as recently proposed by ourselves [ 19 ]. We also divided the patients into three groups using mRS. With regard to the latest variant, we considered the specific characteristics of all the patients with an mRS score of 3 (see Section 4 for details).…”

“…The selected tag SNPs were genotyped with the use of self-designed TaqMan real-time PCR assays. The name of the software used, as well as the description of the components of the PCR reaction mixture and the general cycling conditions, was the same as described in our previous study [ 19 ]. The sequences of the primers and probes used in the current study are presented in Table 4 .…”

“…This involves the exploration of genomic variations in human orthologs of rat genes, which substantially change their expression in the brain in response to transient middle cerebral artery occlusion (tMCAO). We recently demonstrated the efficacy of this method in a pilot study [ 19 ]. In this paper, we present the results obtained using a slightly improved version for the validation of a new set of genes, which were differentially expressed in rats after induced brain ischemia.…”

Special Issue: “Genomics of Stroke”

“…Previously, the authors had developed a bioinformatic approach to exploring single-nucleotide polymorphisms (SNPs) in human orthologues of rat genes expressed differentially under conditions of induced brain ischemia [ 6 ]. Using this approach, the authors identified and analyzed nine SNPs in 553 Russian individuals (331 patients with IS and 222 controls) [ 7 ]. Moreover, Khrunin et al explored the association of SNPs with both IS outcomes and the risk of IS.…”

“…SNPs rs62278647 and rs2316710 (PTX3) were associated significantly with IS ( p = 0.000029 and p = 0.0025, respectively). These correlations for rs62278647 and rs2316710 were found only in women, which suggests a sex-specific association of the PTX3 polymorphism [ 7 ]. Thus, the research of Khrunin et al does 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 [ 7 ].…”