Association of programmed cell death 1 (PD-1) gene polymorphism (rs10204525) with COVID-19 severity and mortality: A case-control study in the Iranian population

BACKGROUND: Programmed cell death 1 (PD-1), as a negative immune regulator, regulates the activation of T cells and maintains the immune system's homeostasis. Previous studies suggest that the effective immune response against COVID-19 contributes to the outcome of the disease. The present study aims to evaluate whether the PD-1 rs10204525 polymorphism is associated with PDCD-1 expression and COVID-19 severity and mortality in the Iranian population. METHODS: The PD-1 rs10204525 was genotyped in 810 COVID-19 patients and 164 healthy individuals as a control group using Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Moreover, we assessed the expression of PDCD-1 in peripheral blood nuclear cells by real-time PCR. RESULTS: Regarding disease severity and mortality, no significant differences were detected between study groups in alleles and genotypes frequency distribution under different inheritance models. We found that the expression of PDCD‐1 was significantly lower in COVID-19 patients with AG and GG genotypes than in the control group. Regarding disease severity, mRNA levels of PDCD‐1 were significantly lower in moderate and critical patients carrying AG genotype than in control (P = 0.005 and P = 0.002, respectively) and mild (P = 0.014 and P = 0.005, respectively) individuals. Additionally, the severe and critical patients with GG genotype displayed a significantly lower level of PDCD-1 compared with the control (P = 0.002 and P < 0.001, respectively), mild (P = 0.004 and P < 0.001, respectively), and moderate (P = 0.014 and P < 0.001, respectively) ones. Regarding disease mortality, the expression of PDCD‐1 was significantly lower in non-survivor COVID-19 patients with GG genotype than in survivors. CONCLUSION: Considering the lack of significant differences in PDCD-1 expression in different genotypes in the control group, lower expression of PDCD-1 in COVID-19 patients carrying the G allele suggests the impact of this single-nucleotide polymorphism on the transcriptional activity of PD-1.