Title:Molecular Determination of Tumor Necrosis Factor-alpha, Interleukin-8,
Interleukin-10, and C-X-C Chemokine Receptor-2 Genetic Variations and
their Association with Disease Susceptibility and Mortality in COVID-19
Patients
Volume: 25
Issue: 1
Author(s): Badr A. Alsayed, Rashid Mir*, Mohammad M. Mir, Tarig M.S. Alnour, Shereen Fawzy, Mesaik M. Ahmed and Dnyanesh Amle
Affiliation:
- Department
of Medical Lab technology Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical
Sciences, University of Tabuk, Tabuk, 71491, Saudi Arabia
Keywords:
Coronavirus disease-2019 (COVID-19), interleukin 8 (IL-8), tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), CXC chemokine receptor-2 (CXCR-2), genetic polymorphisms.
Abstract:
Background: Altered cytokine levels have been associated with poor outcomes among
COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and
CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the
genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find
out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility
to and mortality of COVID-19.
Methods: The present case-control study was conducted on 230 subjects, among whom 115 were
clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects.
The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T
(rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A),
rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility
and mortality was estimated by multivariate analysis. The results were analyzed for risk
of infection and mortality through different inheritance models.
Results: Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A),
rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in
COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients
had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of
IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated
with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes
and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054
CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes
and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality
risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant
protection against mortality from COVID-19.
Conclusion: The findings of this study provide important insights into the COVID-19 disease and
susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073),
IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of
susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger
sample sizes are necessary to confirm our findings.
