Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Effects of TLR-2, TLR-4, Interleukin-6 and -10 Gene Polymorphisms on Preterm Neonates with Early-Onset Sepsis: An Exploratory, Single-Center Study

Version 1 : Received: 30 August 2023 / Approved: 31 August 2023 / Online: 31 August 2023 (05:09:02 CEST)

How to cite: Baizat, M.I.; Iancu, M.; Zaharie, G.; Hasmasanu, M.; Matyas, M.; Rotar, I.C.; Procopciuc, L.M. Effects of TLR-2, TLR-4, Interleukin-6 and -10 Gene Polymorphisms on Preterm Neonates with Early-Onset Sepsis: An Exploratory, Single-Center Study. Preprints 2023, 2023082107. https://doi.org/10.20944/preprints202308.2107.v1 Baizat, M.I.; Iancu, M.; Zaharie, G.; Hasmasanu, M.; Matyas, M.; Rotar, I.C.; Procopciuc, L.M. Effects of TLR-2, TLR-4, Interleukin-6 and -10 Gene Polymorphisms on Preterm Neonates with Early-Onset Sepsis: An Exploratory, Single-Center Study. Preprints 2023, 2023082107. https://doi.org/10.20944/preprints202308.2107.v1

Abstract

Abstract: Background: Neonatal sepsis continues to be one of the leading causes of mortality and morbidity, particularly in under development and underdeveloped countries. We aim to compare laboratory parameters between the early-onset sepsis (EOS) and non-EOS groups and to evaluate the association between TLR2- Arg753Gln, TLR4 -Asp299Gly, IL6-174G/C and IL10-1082G/A gene single nucleotide polymorphisms and EOS susceptibility in preterm newborns. Methods: Genotyping of the TLR2, TLR4, IL6 and IL10 polymorphisms was performed in 36 preterm neonates by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP). Logistic regression analysis was used to test the associations between the studied gene polymorphisms and EOS susceptibility. Results: Statistically significant differences in gestational age and birth weight were observed between the two groups, preterm neonates with EOS having a lower mean of gestational age (weeks, 29.4 ± 2.8 versus 32.6 ± 1.1, p = 0.00002) and lower mean of birth weight (gr., 1342.1 ± 446.5 vs. 1984 ± 376.9) than preterm neonates without EOS. C-reactive protein (CRP) values measured at first day significantly increased in EOS group compared with non-EOS group (median, 95% CI: 0.80 [0.40, 1.15] versus 0.30 [0.02, 0.50]). Mean of neutrophils significantly decreased in the EOS preterm neonates (mean difference: 17.3%, 95% CI: [4.0%, 30.5%], p = 0.0126) and non-EOS group (mean difference: 20.8%, 95% CI: [1.8%, 39.9%, p = 0.0354) between the first day and 7th hospitalization day. The minor IL10-A1082 allele frequency was higher in the EOS group than in the nonEOS group (50% versus 25%) with a marginal statistical significance (p=0.0550). In the dominant model, the A/G + A/A variant genotype of IL10- 1082G/A polymorphism significantly increased the odds of EOS compared with GG genotype (OR= 5.25, p = 0.0322). Conclusions: The results of the current study suggests the IL10- 1082G/A gene polymorphism as significant risk factor for early onset sepsis development in preterm neonates.

Keywords

neonatal sepsis; TLR2-Arg753Gln; TLR4-Asp299Gly; IL6-174G/C; IL10-1082G/A

Subject

Medicine and Pharmacology, Pediatrics, Perinatology and Child Health

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