The association of common glutathione S-transferases polymorphisms with inflammatory and multiorgan impairment biomarkers in COVID-19

Abstract

Introduction: Due to the established role of oxidative stress in the pathophysiology of COVID-19, it has been proposed that inter-individual differences in patients' clinical manifestations might be affected by variations in genes encoding antioxidant enzymes, such as glutathione S-transferases (GSTs). Aim: The aim of this study was to assess the association of polymorphisms in cytosolic GSTs (GSTA1 rs3957357, GSTM3 rs1332018 and GSTP1 rs1695) with inflammatory parameters (leukocytes, lymphocytes, monocytes, C-reactive protein (CRP), fibrinogen, ferritin) and multiorgan impairment biomarkers (urea, creatinine, AST, ALT, LDH) in COVID-19 patients at two-time points. Material and methods: GSTM3, GSTA1 and GSTP1 genotypes were determined in 150 COVID-19 patients by appropriate polymerase chain reaction (PCR) methods. Results: Inflammatory biomarkers (leukocytes, lymphocytes, monocytes) increased 7 days upon admission to the hospital (p < 0.001), while CRP and fibrinogen decreased (p < 0.001). Out of five analyzed multiorgan impairment biomarkers, only urea increased significantly 7 days upon admission (p < 0.007), while AST showed a statistically significant drop (p < 0.001). COVID-19 patients homozygous for variant GSTM3*C/C genotype had increased levels of inflammatory biomarkers such as CRP, fibrinogen and ferritin, but the borderline significance was observed only for fibrinogen (p = 0.057). COVID-19 patients homozygous for variant GSTM3*C allele had the highest levels of ALT (p = 0.021) and LDH (p = 0.045) upon admission. Conclusion: Our results on the association between GSTM3 variant genotype with parameters of systemic inflammation and liver damage in COVID-19 patients can contribute to further understanding of pathophysiological mechanisms underpinning this disease, as well as early recognition of COVID-19 patients prone to worse course of the disease.