Impact of IL-6 rs1800795 and IL-17A rs2275913 Gene Polymorphisms on the COVID-19 Prognosis and Susceptibility in a Sample of Iranian Patients

Background: Elevated levels of interleukin (IL)-6 and IL-17A have been linked to hyper inflammation in COVID-19 patients, and their levels are indicative of the progression of the disease. This study aimed to investigate whether single-nucleotide polymorphisms (SNPs) in IL-6 and IL-17A are linked to COVID-19 susceptibility and prognosis in Iranian patients. Methods: The study enrolled 280 COVID-19 patients, divided into 140 non-severe and 140 severe cases. Genotyping for IL-6 rs1800795 and IL-17A rs2275913 was performed using tetra primer-amplification refractory mutation system-polymerase chain reaction (tetra-ARMS-PCR). IL-6 and IL-17A circulating levels were measured using enzyme-linked immunosorbent assay (ELISA). The study also investigated predictors of COVID-19 mortality. Results: The rs1800795 GG genotype (78/140 (55.7%)) and G allele (205/280 (73.2%)) were significantly associated with a higher risk of severe COVID-19 infection (OR = 2.19, 95%CI: 1.35–3.54, P = .006 and OR = 1.79, 95%CI: 1.25–2.56, P < .001, respectively). The rs1800795 GG genotype was also significantly linked to disease mortality (OR = 1.95, 95%CI: 1.06–3.61, P = .04). In contrast, the rs2275913 GA genotype was found to be protective against severe COVID-19 (OR = 0.5, 95%CI: 0.31–0.80, P = .012), but no significant association was observed with disease mortality. Several predictors of COVID-19 mortality were identified, including INR ≥ 1.2 (OR = 2.19, 95%CI: 1.61–3.78, P = .007), D-dimer ≥ 565.5 ng/mL (OR = 3.12, 95%CI: 1.27–5.68, P = .019), respiratory rate ≥ 29 (OR = 1.19, 95%CI: 1.12–1.28, P = .001), IL-6 serum concentration ≥ 28.5 pg/mL (OR = 1.97, 95%CI: 1.942–2.06, P = .013), and IL-6 rs1800795 GG genotype (OR = 1.95, 95%CI: 1.06–3.61, P = .04). conclusion: The results of this study suggest that the rs1800795 GG genotype and G allele are associated with greater disease severity in COVID-19 patients, while the rs2275913 GA genotype is protective. These findings provide insights into the genetic and molecular mechanisms underlying COVID-19 and may inform the development of more effective therapies and prognostic tools for this disease.