Investigation of the relationship between interleukin-8 (IL-8) (-251 A/T, +781 C/T) gene variations and IL-8 serum expression levels in stroke patients

"Investigation of the relationship between interleukin-8 (IL-8) (-251 A/T, +781 C/T) gene variations and IL-8 serum expression levels in stroke patients", Trakya University, Institute of Health Science, Biophysics Department, Master Thesis, Edirne, 2025. Background and Aim: Cerebrovascular diseases (CVD), particularly ischemic stroke, are major global health problems that lead to high rates of morbidity and mortality. During an ischemic stroke, blockage of cerebral blood vessels results in hypoxia and energy depletion, triggering cellular damage. This process activates inflammatory responses and leads to the release of various cytokines. One of these cytokines, interleukin-8 (IL-8), promotes the migration of neutrophils to the ischemic region, thereby exacerbating inflammation. Elevated IL-8 levels have been associated with increased stroke severity and poor prognosis. The aim of this study was to determine the genotype distributions of the IL-8 gene polymorphisms -251 A/T and +781 C/T, to investigate their relationship with serum IL-8 levels, and to evaluate their potential role in the early diagnosis and progression of ischemic stroke. Materials and Methods: Peripheral venous blood samples were collected from 100 patients diagnosed with stroke and 100 control subjects. DNA isolation was performed from these samples. Genetic susceptibility was determined using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) methods. IL-8 serum expression levels were measured using the ELISA method. The relationships between genetic variations, serum levels, and clinical parameters were evaluated using statistical analyses. Results: In the IL-8 (-251 A/T) gene variation, the TT genotype was found to be more frequent in the stroke group, while the AT genotype was more common in the control group. For the IL-8 (+781 C/T) gene variation, the CC genotype was significantly higher in the stroke group, whereas the TT genotype was more frequent in the control group. Additionally, IL-8 serum expression levels were found to be significantly higher in the stroke group. Conclusion: According to the results of this study, diabetes, hypertension, high cholesterol, heart disease, family history of stroke, and family history of neurodegenerative diseases may represent risk factors for stroke. The TT genotype of the IL-8 (-251 A/T) gene variation may be a potential risk factor for stroke, while the AT genotype may have a protective effect. The presence of the CC genotype in the IL-8 (+781 C/T) gene variation may increase stroke risk, whereas the TT genotype could reduce it. These genetic variations may play an important role as biomarkers and risk assessment parameters in clinical studies. The increase in IL-8 serum expression levels may be a contributing factor to stroke risk and could serve not only as a diagnostic marker but also as a potential prognostic indicator, providing evidence for strategies aimed at reducing brain damage after stroke. The combined evaluation of IL-8 serum expression levels with the CC–CT genotypes of the IL-8 (+781 C/T) gene variation may contribute significantly to the early identification of individuals at risk of stroke and to the implementation of preventive measures. Assessing genetic variations together with serum expression levels may have the potential to play a critical role as a biomarker and risk assessment parameter in identifying stroke risk before disease onset. Keywords: IL-8 (-251 A/T, +781 C/T), gene variations, IL-8 serum expression level Financial Support: The present study was supported by the Research Fund of Trakya University. Project No: 2025/27.