Association between Tumor Necrosis Factor-<i>α</i> Promoter -308 G/A Polymorphism and Early Onset Sepsis in Preterm Infants

Abstract

Early-onset neonatal sepsis (EOS) is diagnosed during the first 7 days of neonatal life and is the major cause of morbidity and mortality among preterm infants. Genetic predisposition may have an impact on EOS susceptibility and outcome. The aim of our study was to explore the association between TNF-α-308 G/A or IL-6-174 G/C gene polymorphism and the susceptibility and outcome of EOS in preterm infants. The study included 471 preterm infants: 282 with EOS (151 with culture proven sepsis and 131 with clinical sepsis) and 189 without infection (control group). TNF-α-308 G/A and IL-6-174 G/C were genotyped using Real-time RCR method. We observed significantly higher frequency of A allele of TNF-α-308 G/A polymorphism in blood culture proven EOS (p = 0.017) or clinical EOS (p = 0.025) compared with the control group. Logistic regression confirmed significant association between TNF-α-308 GA+AA genotypes and development of culture proven EOS (B =-0.718, p = 0.013) or clinical EOS (B =-0.602, p = 0.027). No significant differences in IL6-174G/C alleles or genotypes distribution have been observed between culture proven EOS group, clinical EOS group and the control group. An association between TNF-α-308 G/A or IL-6-174 G/C genotypes and EOS lethal outcome was not observed (p = 0.652 and p = 0.384, respectively). According to our analysis of large cohort of preterm infants with clearly defined EOS groups, the TNF-α-308 A allele may be a risk factor for the EOS occurrence.

Association between Interleukin-6 rs1800795 Polymorphism and Serum Interleukin-6 Levels and Full-Term Neonatal Sepsis

“…The current study showed that there is no statistically significant difference between IL-6 rs1800795 polymorphisms, indicating that the IL-6 rs1800795 G/C polymorphism had no significant association with the risk of sepsis in full-term neonates. Varljen et al 16 found no association between the genotypes or alleles of IL-6 rs1800795 G/C polymorphism and early-onset sepsis in premature infants, in agreement with the results of this study regarding full-term neonatal sepsis. The results of a meta-analysis by some researchers 17 18 showed that IL-6 rs1800795 G/C polymorphism was not associated with the risk or mortality of sepsis in any age or ethnic group.…”

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“…The current study showed that there is no statistically significant difference between IL-6 rs1800795 polymorphisms, indicating that the IL-6 rs1800795 G/C polymorphism had no significant association with the risk of sepsis in full-term neonates. Varljen et al 16 found no association between the genotypes or alleles of IL-6 rs1800795 G/C polymorphism and early-onset sepsis in premature infants, in agreement with the results of this study regarding fullterm neonatal sepsis. The results of a meta-analysis by some researchers 17,18 showed that IL-6 rs1800795 G/C polymorphism was not associated with the risk or mortality of sepsis in any age or ethnic group.…”

Tumor necrosis factor-α small interfering RNA alveolar epithelial cell-targeting nanoparticles reduce lung injury in C57BL/6J mice with sepsis

“…25 It controls the promoters of nearly 200 genes stimulated by LPS and inflammatory factors, and its downstream genes such as IL-1b and IL-6 are involved in the development of sepsis. 26 Several studies [27][28][29] have reported increased TNF-a activity in sepsis models and the lung tissues of patients with sepsis. This activity is related to the severity of lung injury, so inhibiting TNF-a expression effectively inhibits the downstream signaling pathway, thus reducing lung injury and improving the survival rate.…”