[A study of genetic variants in patients with ischemic stroke in human rat gene orthologues]

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 (LGALS3) was associated with negative IS outcomes (p=0.048). SNPs rs62278647 and rs2316710 (PTX3) were significantly associated with IS risk (p=0.000029 and p=0.0025, respectively). The associations for rs62278647 and rs2316710 were found only in females, suggesting a gender-related PTX3 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.