Correlation of P352L, R538G Col4A1 Gene, RS951733 Col4A2 Gene Locus Polymorphisms, IFN-, IL-17, and VE-Cadherin Levels with the Event of Non-Lobar Spontaneous Intracerebral Hemorrhage in Hypertension Patients: Research Protocol (Preprint)

Abstract

Background: Stroke is an acute and focal neurological deficit syndrome. By definition, it can be interpreted as a clinical syndrome resulting from vascular injury (infarction, bleeding) in the central nervous system. Hypertension is the main risk factor of non-lobar intracerebral hemorrhage (ICH), in which around 85% of ICH patients are hypertensive. Hypertension is often found to damage the basement membrane of blood vessel walls. It can also induce tissue injury by increasing the inflammatory cytokines IL 17 and IFN-γ and reducing the expression of VE-Cadherin. Genetically, mutation of the genes Col4A1 and Col4A2 has been correlated with the incidence of non-lobar intracerebral hemorrhage.

Objective: The aim is to investigate the correlation between the P352L, R538G Col4A1 gene, RS9521733 Col4A2 gene locus polymorphisms, levels of IFN-γ, IL-17, and VE-Cadherin with the event of non-lobar spontaneous intracerebral hemorrhage in hypertensive patients.

Method: This is a research protocol. This research will be an observational study with a comparative cross-sectional approach where the dependent and independent variables will be examined at the same time. This research was designed to investigate the correlation between the P352L, R538G Col4A1 gene, RS9521733 Col4A2 gene locus polymorphisms, level of IFN-γ, IL-17, and VE-Cadherin with the incident of spontaneous non-lobar intracerebral hemorrhage in hypertensive patients. Blood samples will be collected from hypertensive patients with non-lobar intracerebral hemorrhage stroke patients with hypertension and hypertensive patients without intracerebral hemorrhage. The samples will be analyzed using ELISA and transcription polymerase chain reaction (PCR). Data analysis will involve statistical tests with descriptive analysis, univariate analysis, and bivariate analysis.

Results: This research is at the protocol development stage. A pilot study regarding its feasibility has been completed in January 2023. The results of the study are expected to be available by the end of 2024.

Conclusion: A study of the relationship between Col4A1, Col4A2 gene polymorphisms, levels of IFN-γ, IL-17, and VE-Cadherin on the incidence of non-lobar intracerebral hemorrhage in hypertension patients is expected to increase understanding and expand knowledge of the pathophysiology of the risk of non-lobar intracerebral hemorrhage in hypertension patients.