Effect of IL-2 T-330G polymorphism on markers of systemic inflammation, intestinal permeability and vascular regulation in post-COVID patients

Recent studies suggest a role of genetic factors, i.e., polymorphisms of genes controlling the main immune components of antiviral response, and the risk of COVID-19 infection, severe course and lethal outcomes of the disease, as well as development of clinical or laboratory changes in the post-COVID period. Interleukin-2 (IL-2) plays an important role in immunopathology of COVID-19. However, there are only few data on the impact of single nucleotide polymorphisms, e.g., IL-2 330T/G (rs2069762) gene variant on molecular changes during the post-COVID period. The aim of our study was to investigate differences in systemic inflammation markers, intestinal permeability and vascular regulation in patients with post-COVID syndrome, and single nucleotide polymorphisms (SNPs) of the IL-2 330T/G gene. Fiftyfour patients (28 females (51.85%) and 26 males (48.15%), mean age 45.6±6.14 years) who suffered with COVID-19 were included into the study. The patients were tested for IL-2 T-330G polymorphism by allelespecific polymerase chain reaction (PCR) with electrophoretic detection of products. PCR was performed using the IL-2 T-330G kit (LLC "Litech", Russia). The contents of C-reactive protein (CRP, mg/L), lipopolysaccharide-binding protein (LBP, ng/mL), tissue plasminogen activator (tPA, ng/mL), zonulin (ng/ mL), endothelin-1 (pg/mL), and angiotensin-2 (pg/mL) in blood plasma were determined by ELISA test manufactured by Cloud Clone Corp. (Wuhan, Hubei, China). The patients harboring a homozygous GG variant of T-330G IL-2 gene polymorphism showed significantly lower CRP levels than in the heterozygous TG group (p = 0.013), and TT homozygous group (p = 0.039). The tPA levels were significantly higher in the GG homozygote group compared to TT homozygotes (p = 0.017). The highest zonulin values were recorded in the TG heterozygote group, compared to TT homozygotes (p = 0.013). The highest angiotensin-2 values were found in the homozygous TT group (p < 0.05). No significant variations of LBP and endothelin-1 were registered between the studied groups. The T-330G polymorphism of IL-2 gene is, therefore, associated with some molecular changes in the post-COVID period, which may potentially influence both clinical manifestations of post-COVID syndrome, and its long-term consequences in future. Further in-depth studies of T-330G effects upon activity of the IL-2 gene and related molecular events is necessary in order to understand the clinical aspects of post-COVID syndrome. 

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