Toll-like receptors (TLR) 2, 3, and 4 gene polymorphisms in critically ill patients

Abstract

Considering that TLR2, TLR3 and TLR4 play very important roles in inflammatory processes, the question arises whether the presence of polymorphisms in these genes is associated with susceptibility to sepsis. The aim of this study was to examine the association of TLR2, TLR3 and TLR4 polymorphisms with clinical characteristics and outcome of critically ill patients. A follow-up study was conducted on 121 critically ill Caucasian Serbian patients. Five polymorphisms in TLRs, TLR2 (rs5743708), TLR3 (rs3775291, rs5743312) and TLR4 (rs4986790, rs4986791) were genotyped by real-time PCR. Investigated polymorphisms in TLR2 and TLR4 were not associated with the clinical characteristics and outcome of critically ill patients. TLR3 rs3775291 polymorphism was associated with patient's outcome (p=0.018). Patients with sepsis and a TLR3 rs3775291-mutated genotype had a four-fold higher mortality rate compared to wild type and heterozygous carriers. Multivariate regression analysis showed that age, sex and TLR3 rs3775291 polymorphism are independent variables of the outcome of critically ill patients. For the first time, our preliminary findings indicate the role of TLR3 with MyD88 independent signaling and its polymorphism (TLR3 rs3775291) in sepsis and survival in critically ill Serbian patients.