The role of single nucleotide polymorphisms in predicting individual stroke risk

Abstract

Background. In the context of predictive medicine, personalized assessment of ischemic stroke risk based on molecular genetic testing is becoming increasingly relevant. Polymorphisms in folate cycle genes (MTHFR, MTR, MTRR), leading to hyperhomocysteinemia, cause endothelial dysfunction and accelerate atherogenesis. The role of the renin-angiotensin system (RAS) is no less important: genetic variations in the AGT and NOS3 genes are associated with arterial hypertension and altered vascular tone, which creates a predisposition to cerebrovascular accidents. Objective. To identify associations between polymorphisms of folate cycle and renin-angiotensin system genes and the development of acute ischemic stroke and transient ischemic attack (TIA). Methods. The observational study included 492 patients who were treated in hospital at the Institution Clinical Hospital No. 1 of the Presidential Administration of the Russian Federation in the period 2022–2025 and who signed informed consent for molecular genetic testing. A comparative analysis of clinical, laboratory, instrumental, and molecular genetic data (polymorphisms of MTHFR, MTR, MTRR, AGT, NOS3, and AGTR1) was performed between the ischemic stroke group (n=426) and the TIA group (n=66). Statistical analysis was carried out using the Mann-Whitney U test and Pearson's chisquared test. Results. Stroke patients were older (73 vs 66 years, p=0.005) and more frequently male (43.4 % vs 27.3 %, p=0.013). The stroke group had significantly higher triglyceride levels (p < 0.001) and potassium levels (p < 0.001), as well as a higher frequency of pathological MRT findings (p < 0.001). Genetic analysis revealed a significant predominance in the stroke group of homozygous CC genotypes for MTHFR C677T (p=0.001), AGT174 (p=0.004), AGT235 (p < 0.001), and NOS3 (p=0.028). In contrast, the TIA group more frequently carried TT genotypes for C677T AGT235, and NOS3, as well as the heterozygous CT genotype for AGT174. Conclusion. Molecular genetic testing of polymorphisms in folate cycle and renin — angiotensin system genes represents a promising tool for risk stratification and differential diagnosis of ischemic stroke versus TIA, and may serve as a foundation for personalized pharmacotherapy in the nearest future.