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


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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 RegistrationClinicalTrials.gov identifier: NCT00932243HighlightsCommon TLR4 polymorphisms in Central Greece present similar incidence with other critically-ill populations.Instead, TLR2-Arg753Gln polymorphism demonstrates unexpectedly low prevalence in our specific population.TLR4-Asp299Gly and TLR4-Thr399Ile polymorphisms usually coincide in Central Greece.TLR4-Asp299Gly and TLR4-Thr399Ile may be related to specific Gram-negative multi-drug resistant ICU-acquired infections.Common TLR polymorphisms are not associated with either the incidence or the time-course characteristics of septic shock.TLR4 polymorphisms may be associated with prolonged ICU stay.

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