The regulatory toll-like receptor 4 genetic polymorphism rs11536889 is associated with renal, coagulation and hepatic organ failure in sepsis patients

Abstract

BackgroundToll-like receptor 4 (TLR4), a lipopolysaccharide (LPS) receptor complex signal-transducing molecule, plays a crucial role in sensing LPS from gram-negative bacteria. TLR4 signaling pathway activation by LPS plays a major role in sepsis pathogenesis. A single nucleotide polymorphism, rs11536889, in the 3’-untranslated region of the TLR4 gene is thought to affect TLR4 translation. This study aimed to investigate whether organ failure in sepsis patients is related to the TLR4 rs11536889 genotype.MethodsAdult Caucasian patients with sepsis from the intensive care unit of a university medical center were followed up for 90 days, and organ failure was recorded as the primary outcome variable. Blood samples were collected at enrollment for TLR4 rs11536889 genotyping. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure.ResultsA total of 210 critically ill patients with sepsis were enrolled into this study. Wild-type GG was compared to GC/CC. During their stay in the intensive care unit, GG patients presented significantly higher SOFA scores than did C allele carriers (7.9 ± 4.5 and 6.8 ± 4.2, respectively; p = 0.0005). Analysis of organ-specific SOFA sub-scores revealed significant differences in three organ systems: renal, coagulation and hepatic (p = 0.0005, p = 0.0245 and p < 0.0001, respectively). Additionally, the rs11536889 polymorphism was associated with a higher incidence of gram-negative infections.ConclusionsThese results offer the first evidence that TLR4 rs11536889 is a useful marker of organ failure in patients with sepsis.

Primary bacteraemia is associated with a higher mortality risk compared with pulmonary and intra-abdominal infections in patients with sepsis: a prospective observational cohort study

“…As described previously, 28 29 the patient exclusion criteria were the following: (1) age less than 18 years; (2) being pregnant or nursing an infant; (3) immunosuppressive therapy (eg, cyclosporine or azathioprine) or cancer-related chemotherapy; (4) documented or suspected acute myocardial infarction within the previous 6 weeks; (5) a history of New York Heart Association functional class IV chronic heart failure; (6) HIV infection; (7) a do not resuscitate or do not treat order or the patient and/or his or her legal representative not being committed to aggressive management; (8) not being expected to survive the 28-day observation period or not being likely to be placed on life support because of an uncorrectable medical condition, including a poorly controlled neoplasm or end-stage lung disease; (9) a chronic vegetative state or a similar long-term neurological condition; (10) current participation in any interventional study (of a drug or device); (11) inability to be fully evaluated during the study period and (12) being a study-site employee or a family member of a study-site employee involved in conducting this study.…”

The relationship between toll like receptor 4 gene rs4986790 and rs4986791 polymorphisms and sepsis susceptibility: A meta-analysis

“…Besides, Mansur et al . put forward in their study that the polymorphism rs11536889 in this gene was associated with renal, coagulation and hepatic organ failure in sepsis patients44. In addition, a study by Nachtigall et al .…”

The role of genetics and antibodies in sepsis

“…The salient SNP in this haplotype seems to be rs11536889 since presence of only G alleles was found in Chinese patients to be associated with greater sequential organ failures assessment (SOFA) scores for renal, liver and coagulation function. However, overall survival compared to patients bearing at least one C allele remained unchanged (21).…”