# Exploratory Analysis of TLR2, TLR4, Interleukin 6 and Interleukin 10 Gene Polymorphisms in Relation to Clinical Early-Onset Sepsis in Preterm Neonates: A Single-Center Study

## TL;DR

This study explores how gene variations in TLR2, TLR4, IL6, and IL10 relate to early-onset sepsis in preterm babies.

## Contribution

The study identifies a potential link between IL10 gene polymorphism and early-onset sepsis in preterm neonates.

## Key findings

- Preterm neonates with clinical EOS had lower gestational age and birth weight.
- CRP levels were higher in the clinical EOS group on the first day of hospitalization.
- The IL10-1082G/A polymorphism increased the odds of clinical EOS in a dominant model.

## Abstract

(1) Background: Neonatal sepsis continues to be one of the leading causes of mortality and morbidity, particularly in underdeveloped countries. We aimed to compare laboratory parameters between clinical early-onset sepsis (clinEOS) and NNNon-clinEOS groups and to evaluate the association between TLR2-Arg753Gln, TLR4-Asp299Gly, IL6-174G/C, and IL10-1082G/A gene single-nucleotide polymorphisms and clinical EOS susceptibility in preterm newborns. (2) Materials and Methods: Genotyping of the TLR2, TLR4, IL6, and IL10 polymorphisms was performed in 36 preterm neonates with 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. (3) Results: Statistically significant differences in gestational age and birth weight were observed between the two groups, with preterm neonates with clinical EOS having a lower mean gestational age (mean (SD): 29.4 (2.8) weeks vs. 32.6 (1.1); p = 0.00002) and a lower mean birth weight (1342.1 (446.5) gr. Vs. 1984 (376.9)) than preterm neonates without clinical EOS. C-reactive protein (CRP) values measured on the first day significantly increased in the clinEOS group compared with the non-clinEOS group (median, 95% CI: 0.80 [0.40, 1.15] vs. 0.30 [0.02, 0.50]). The mean number of neutrophils significantly decreased in the preterm neonates with clinical EOS (mean difference: 17.3%; 95% CI: [4.0%, 30.5%]; p = 0.0126) and non-clinEOS group (mean difference: 20.8%; 95% CI: [1.8%, 39.9%]; p = 0.0354) between the first and seventh hospitalization days. In the dominant model, the A/G + A/A variant genotype of the IL10-1082G/A polymorphism significantly increased the odds of clinical EOS compared with the GG genotype (OR = 5.25; p = 0.0322), but the gestational-age-group adjusted model yielded p = 0.0752. (4) Conclusions: The results of the current study suggest that IL10-1082G/A gene polymorphism is a significant risk factor for clinical early-onset sepsis development in preterm neonates, but there was no evidence of a gestational age-group independent direct effect of IL10-1082G/A gene polymorphism on clinical EOS susceptibility. The results should be considered as exploratory.