title: Toll-like receptor 4 polymorphisms and the risk of gram-negative bacterial infections after liver transplantation.
abstract: BACKGROUND
  Toll-like receptor 4 (TLR4) is the main immune molecule that recognizes lipopolysaccharide from gram-negative bacteria. Single-nucleotide polymorphisms (SNPs) in the TLR4 gene that impair lipopolysaccharide recognition may influence gram-negative bacterial infections after liver transplantation.
  
  
  METHODS
  TLR4 D299G and T399I SNPs were assessed in a cohort of 706 liver transplant recipients and were associated with the clinical characteristics and outcome of gram-negative bacterial infections. Cox proportional hazard model was performed to determine covariates associated with outcomes after gram-negative bacterial infections.
  
  
  RESULTS
  Of 706 patients, there were 108 with microbiologically confirmed gram-negative bacterial infections, 135 with clinically suspected but not confirmed infections, and 463 patients without gram-negative bacterial infections. The proportions of TLR4 D299G (5/108 [4.6%] vs. 32/463 [6.9%]; P=0.39) and T399I SNPs (19/108 [17.6%] vs. 68/463 [14.7%]; P=0.45) did not differ between those with or without microbiologically confirmed gram-negative bacterial infections. Female gender (odds ratio 2.30, 95% confidence interval [CI]1.50-3.53; P<0.001) and ulcerative colitis (odds ratio 2.18, 95% CI 1.08-4.38; P=0.03) were associated with gram-negative bacterial infections. Among 108 patients with gram-negative bacterial infections, alcoholic liver disease (relative risk [RR] 4.87, 95% CI 1.54-15.44; P=0.007), initial septic shock (RR 10.19, 95% CI 2.70-38.37; P=0.001), and nosocomially-acquired infection (RR 4.61, 95% CI 1.51-14.14; P=0.007) were significantly associated with 90-day mortality after gram-negative bacterial infections. In contrast, TLR4 D299G and T399I SNPs were not significantly associated with mortality after gram-negative bacterial infections.
  
  
  CONCLUSIONS
  In this cohort of liver transplant recipients with long-term follow-up, no significant association was observed between TLR4 D299G and T399I SNPs and the risk and outcome of gram-negative bacterial infections.
authors.affiliation: Division of Infectious Diseases, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Sang-Oh
authors.initials: SO
authors.lastname: Lee
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brown
authors.forename: Seung H
authors.initials: SH
authors.lastname: Kang
authors.forename: Rima C
authors.initials: RC
authors.lastname: Abdel Massih
authors.forename: Raymund R
authors.initials: RR
authors.lastname: Razonable
mesh_terms: D000328:Adult; D001424:Bacterial Infections / Q000150:complications / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006090:Gram-Negative Bacteria / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D007107:Immune System; D008070:Lipopolysaccharides / Q000378:metabolism; D017093:Liver Failure / Q000150:complications / Q000628:therapy*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications; D016016:Proportional Hazards Models; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4