Study of polymorphism of human genes, orthologues of which are functionally involved in the response to experimental brain ischemia in model systems

In a model of experimental rat brain ischemia caused by the right transient middle cerebral artery occlusion using RNA-Seq and real-time PCR, genes that significantly change their activity in the rat brain were revealed. For 38 most active rat genes their human orthologous genes were identified. Using the genotype data from the 1000 genome project (CEU population), we explored the polymorphism of each of the genes and identified the loci showed the maximum number of associations with other polymorphisms (tagSNPs). At the first stage, the polymorphisms in DRD2, CCL23, SOCS3, HSPB1 and CHRM genes were studied. From one to three tagSNPs were selected for further analysis in each gene. Using TaqMan real-time PCR assays, allelic variants of the selected loci were genotyped in 100 patients with ischemic stroke and in 100 controls. In the most cases the frequencies of genotypes of the SNPs in the control group were similar to those in the group of patients with ischemic stroke. The most substantial differences in the distribution of genotypes between the groups (p = 0.088) were demonstrated for the SNP rs8069976 from the region of SOCS3 gene. To clarify the direction of the differences revealed, their testing in the patient and control samples of larger sizes is planned.

ишемический инсульт, полиморфизм ДНК, геном человека, транскриптом крысы, ischemic stroke, DNA polymorphism, human genome, rat transcriptome