Toll-like receptor 2, 4 and 9 polymorphisms and their association with ICU-acquired infections in Central Greece

Abstract

Purpose: To test the potential of four common Toll-like receptor (TLR) polymorphisms to predispose to specific intensive care unit (ICU)-acquired infections and affect outcomes in a Greek ICU. Materials and methods: The incidence of TLR2-Arg753Gln, TLR4-Asp299Gly, TLR4-Thr399Ile and TLR9-T1237C polymorphisms, and their association with ICU-acquired infections and patients' clinical outcomes were prospectively evaluated The examined genetic polymorphisms were assessed by real-time Polymerase-Chain-Reaction (PCR). Results: During a 15-month period, 224 patients were enrolled and genotyped. The prevalence of genetic polymorphisms for TLR4-Asp299Gly, TLR4-Thr399Ile, mixed TLR4-Asp299Gly/Thr399Ile, TLR9-T1237C and TLR2-Arg753Gln was 14.4%, 14.7%, 11.2%, 24.5% and 2.2%, respectively. TLR4 polymorphisms were associated with increased susceptibility towards specific ICU-acquired infections, i.e. Gram-negative central-nervous-system infections (CNSI), ventilator-associated pneumonia (VAP) and urinary-tract infections (UTI), principally due to multi-drug resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumonia, respectively (all P < 0.05). TLR9-T1237C polymorphism was associated with lower incidence and fewer relapses of CNSIs and UTIs when compared to mixed TLR4-Asp299Gly/Thr399Ile polymorphism group (P ≤ 0.039). ICU-stay was significantly prolonged in TLR4 polymorphisms (P ≤ 0.0416). Conclusions: Common TLR-signaling polymorphisms might be implicated in the clinical phenotype of ICU-acquired infections in Central Greece. The possible impact of TLR4 polymorphisms on enhanced susceptibility towards Gram-negative MDR-infections in defined critical-disease states warrants further investigation. Trial Registration Clinical Trials.gov identifier: NCT00932243 © 2018