Article

Thrombophilia and Folate Cycle Gene Polymorphisms in the Development of Ischemic Stroke After COVID-19

Dildora KadirovnaDepartment of Neurology and Medical Psychology, Tashkent State Medical University, Farabi Street 2, Tashkent 100109, UzbekistanNodirjon Kadirovich KhaydarovDepartment of Neurology and Medical Psychology, Tashkent State Medical University, Farabi Street 2, Tashkent 100109, UzbekistanSanobar Nizamovna RakhmatovaDepartment of Neurology, Bukhara State Medical Institute, Gijduvan Street, 23, Bukhara 100100, UzbekistanNilufar Kahhorovna SalomovaDepartment of Neurology, Bukhara State Medical Institute, Gijduvan Street, 23, Bukhara 100100, UzbekistanVisola Furkatovna GaffarovaDepartment of Neurology, Bukhara State Medical Institute, Gijduvan Street, 23, Bukhara 100100, UzbekistanQunduz Abdullo Qizi SadulloyevaDepartment of Neurology, Bukhara State Medical Institute, Gijduvan Street, 23, Bukhara 100100, UzbekistanDilshod Izbilloyevich SadullayevDepartment of Neurology, Bukhara State Medical Institute, Gijduvan Street, 23, Bukhara 100100, UzbekistanMukhammadjon Kahramon Ugli BerdiyevDepartment of Neurology, Bukhara State Medical Institute, Gijduvan Street, 23, Bukhara 100100, UzbekistanBakhodir Igamovich DjumayevDepartment of Neurology, Bukhara State Medical Institute, Gijduvan Street, 23, Bukhara 100100, UzbekistanNodirabegim Akbarovna ShukrulloevaDepartment of Neurology, Bukhara State Medical Institute, Gijduvan Street, 23, Bukhara 100100, UzbekistanFerangiz Shuxratovna MukhamadievaDepartment of Neurology, Bukhara State Medical Institute, Gijduvan Street, 23, Bukhara 100100, UzbekistanIbodov Bekzod AbdusattotovichDepartment of Neurology and Medical Psychology, Tashkent State Medical University, Farabi Street 2, Tashkent 100109, UzbekistanDilbar KhodjievaDepartment of Neurology, Bukhara State Medical Institute, Gijduvan Street, 23, Bukhara 100100, Uzbekistan

International Journal of Molecular Sciencesjournal2026en

ABI

Abstract

COVID-19 not only affects the respiratory system but also increases the risk of cerebrovascular complications, including ischemic stroke. Experimental and clinical data suggest that cytokine dysregulation and polymorphisms of thrombophilia-related genes (MTHFR, MTR, and MTRR) may jointly promote hypercoagulation, endothelial dysfunction, and thromboinflammation, thereby contributing to post-COVID ischemic stroke. This study included 160 patients treated at Zangiota Infectious Diseases Hospitals (2021–2023): 60 patients with ischemic stroke in the acute or post-COVID period (experiment group), 50 COVID-19 patients without ischemic stroke (comparison group), and 50 ischemic stroke patients without COVID-19 (control group). Clinical–neurological and immunological parameters were assessed, and polymorphisms in thrombophilia/folate cycle genes (MTHFR C677T, MTR, and MTRR) were genotyped by PCR/real-time PCR. Statistical analysis included χ2 tests, t-tests, logistic regression with odds ratios (OR) and 95% confidence intervals (CI); Hardy–Weinberg equilibrium was verified. A strong association was identified between the MTHFR C677T polymorphism and ischemic stroke on the background of COVID-19 (OR = 5.4; 95% CI: 2.1–13.8; p < 0.001). The TNF-α rs1800629 polymorphism was also significantly associated with COVID-19-related cerebrovascular events (OR = 3.27; 95% CI: 1.4–7.6; p = 0.006). Carriage of two or more minor alleles produced a synergistic effect, markedly increasing the risk of post-COVID ischemic stroke (OR = 5.59; 95% CI: 2.3–13.6; p < 0.001). These polymorphisms were linked to hyperhomocysteinemia, endothelial dysfunction, and mechanisms contributing to multifactorial arterial ischemic events. The combined assessment of thrombophilia and folate cycle-related genotypes and clinical indicators may provide a potential framework for improved risk stratification. Polymorphisms in MTHFR may appear to represent important genetic determinants of ischemic stroke following COVID-19, particularly in the context of arterial ischemic mechanisms.

Topics

Long-Term Effects of COVID-19 COVID-19 Clinical Research Studies Acute Ischemic Stroke Management

Identifiers

DOI: 10.3390/ijms27062650

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