Tumor Necrosis Factor Alpha Gene Polymorphisms Increase Susceptibility to Adenovirus Infection in Children and Are Correlated with Severity of Adenovirus-Associated Pneumonia

Abstract

Objective: To study the relationships between single nucleotide polymorphisms (SNPs) in the intron of the tumor necrosis factor α (TNFα) gene and the susceptibility and severity of disease associated with adenovirus infection in children. Methods: Four polymorphic loci of the TNFα gene (rs3093661, rs1800610, rs3093662, and rs3093664) were characterized allelically and genotypically in 320 children with adenovirus-associated pneumonia (AP) and compared with 320 healthy controls. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the plasma TNFα protein levels in all subjects. Results: The TNFα gene rs3093661 locus A allele, the rs1800610 locus A allele, the rs3093662 locus G allele, and the rs3093664 locus G allele were identified as susceptibility alleles for development of AP, and they were also positively correlated with the severity of AP. In children who had the GGAA haplotype, AP susceptibility was significantly reduced (0.28-fold) (95% confidence interval, CI: 0.20-0.40, p < 0.001). Conversely, among the subjects with the AGGG haplotype, their AP susceptibility risk was significantly increased (2.76-fold) (95% CI: 1.77-4.29, p < 0.001); and in the subjects with the AP GGGG haplotype their AP susceptibility risk was significantly increased (2.49-fold) (95% CI: 1.67-3.72, p < 0.001). The TNFα rs3093661, rs1800610, rs3093662, and rs3093664 SNPs were significantly correlated with plasma TNFα levels (p < 0.05). Conclusion: The TNFα gene rs3093661, rs1800610, rs3093662, and rs3093664 loci are associated with AP susceptibility and severity. This relationship might be due to the effect on TNFα levels found in the plasma. Clinical Trial Registration number: LL20190723.