1. Introduction

Ischemic stroke is a leading cause of disability and death worldwide, posing significant challenges to healthcare systems due to its complex etiology and varied clinical presentations. Understanding the genetic underpinnings of ischemic stroke is crucial for developing targeted preventive and therapeutic strategies. Recent advances in molecular genetics have identified various genetic markers associated with increased risk of ischemic stroke, providing new insights into its pathogenesis.

Genetic polymorphisms, particularly single nucleotide polymorphisms (SNPs), have been implicated in the development of ischemic stroke. These genetic variations can influence the expression and function of proteins involved in critical biological pathways such as angiogenesis, vascular integrity, and hypoxia response. Specifically, genes such as VEGF (vascular endothelial growth factor) and HIF-1α (hypoxia-inducible factor 1-alpha) have garnered attention due to their roles in vascular health and response to ischemic conditions.

Several studies have explored the relationship between genetic polymorphisms and ischemic stroke. For instance, a study by Hăşmăşanu et al. (2023) examined the association between the VEGF gene polymorphism and ischemic stroke, finding significant links between certain SNPs and increased stroke risk [3]. Another study by Vokhidova et al. (2020) identified polymorphisms in the HIF-1α gene as potential risk factors for ischemic stroke, highlighting the gene's role in hypoxia response and vascular adaptation [10]. Additionally, a meta-analysis by Lindgren et al. (2014) reviewed multiple studies on genetic variations in stroke-related genes, confirming the importance of genetic predisposition in ischemic stroke susceptibility [4]. These findings underscore the relevance of genetic research in understanding and managing ischemic stroke.

The primary motivation for this study is to elucidate the genetic predictors of ischemic stroke by analyzing the frequency of SNPs in candidate genes among patients with primary and recurrent ischemic stroke. Identifying these genetic markers can enhance our understanding of stroke pathophysiology, potentially leading to improved risk assessment and personalized treatment approaches.

The aims of this study are threefold: first, to determine the association between specific SNPs in VEGF and HIF-1α genes and the risk of ischemic stroke; second, to compare the frequency of these SNPs between patients with primary and recurrent ischemic stroke; and third, to assess the potential protective or risk-modifying effects of these genetic variations.

2. Mаteriаls аnd Methоds

The study involved molecular-genetic analyses conducted in a specialized laboratory at the Republican Scientific Center of Hematology. We analyzed the following polymorphic sites: VEGF 634 G/C rs2010963, VEGF 2578C/A, and HIF-1α P582S (C1772T) rs11549465. The study included 93 patients with ischemic stroke, divided into primary stroke (46 patients) and recurrent stroke (47 patients) subgroups, along with 91 healthy controls. Blood samples were collected and analyzed for SNP frequencies. Genetic analyses were performed using PCR and sequencing technologies to identify SNPs in the targeted genes.

DNA Extraction and Genotyping. Peripheral blood samples were collected from all participants. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit (Qiagen, Germany) according to the manufacturer’s instructions. The concentration and purity of the extracted DNA were measured using a NanoDrop spectrophotometer (Thermo Fisher Scientific, USA).

Statistical Analysis. Genotype frequencies were compared between ischemic stroke patients and controls using chi-square tests. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to assess the association between each SNP and the risk of ischemic stroke. A p-value < 0.05 was considered statistically significant. All statistical analyses were performed using SPSS software version 25.0 (IBM, USA).

3. Result аnd Discussiоn

Table 1. Genotype Frequencies and Association with Ischemic Stroke for VEGF 634 G/C rs2010963

Table 2. Genotype Frequencies and Association with Ischemic Stroke for VEGF 2578C/A

Table 3. Genotype Frequencies and Association with Ischemic Stroke for HIF-1α P582S (C1772T) rs11549465

The genetic analysis of ischemic stroke patients and control subjects provided significant insights into the role of specific SNPs in stroke susceptibility. Our findings support the hypothesis that genetic variations in VEGF and HIF-1α genes are associated with ischemic stroke risk. This discussion contextualizes our results within the broader scientific literature, comparing and contrasting findings from various studies to highlight the significance of our research.

The VEGF 634 G/C rs2010963 polymorphism has been widely studied in the context of ischemic stroke. Our study found that the C/C genotype was significantly more frequent in the ischemic stroke group compared to controls, suggesting an increased risk associated with this genotype. This finding aligns with the results of Hăşmăşanu et al. (2023), who also reported a significant association between VEGF polymorphisms and ischemic stroke risk [3]. Moreover, a study by Xu et al. (2019) confirmed the association of VEGF gene variants with stroke susceptibility in a Chinese population, reinforcing our results [8].

In our study, the VEGF 2578C/A polymorphism showed that the C/C genotype was more common in the control group, indicating a potential protective effect. Similar protective associations have been observed by Qiu et al. (2016), who highlighted the role of VEGF polymorphisms in vascular health [6]. Additionally, the meta-analysis by Zhang et al. (2024) supported the protective role of certain VEGF gene variants in reducing stroke risk [11].

The HIF-1α P582S (C1772T) rs11549465 polymorphism was also significant in our study, with the C/C genotype being more frequent in controls, suggesting a protective role. This finding is consistent with the study by Mitroshina et al. (2021), which linked HIF-1α polymorphisms to ischemic stroke through mechanisms involving hypoxia response [5]. Furthermore, a study by Amalia et al. (2020) demonstrated that HIF-1α polymorphisms are critical in the pathogenesis of ischemic stroke, corroborating our results [1].

The comparative analysis of our findings with existing literature reveals a consistent pattern of associations between specific genetic polymorphisms and ischemic stroke risk. For example, studies by Traylor et al. (2012) and Hăşmăşanu et al. (2023) have shown that genetic variations in VEGF and related pathways significantly influence stroke risk [3] [7]. Similarly, research by Dong et al. (2018) and Yang et al. (2018) underscores the importance of genetic predisposition in stroke susceptibility, particularly involving hypoxia-inducible factors [2] [9].

While our study provides valuable insights, it is important to acknowledge its limitations. The sample size, although adequate, may not capture all genetic variations associated with ischemic stroke. Future research should aim to replicate these findings in larger, more diverse populations to validate the associations observed. Additionally, functional studies are needed to elucidate the precise biological mechanisms through which these genetic polymorphisms influence stroke risk.

4. Conclusions

Our findings suggest significant associations between specific SNPs and ischemic stroke risk. The VEGF 634 G/C and HIF-1α P582S (C1772T) genotypes, in particular, show potential as genetic markers for stroke susceptibility. Further research is needed to confirm these associations and explore their implications for stroke prevention and management.