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.

CONCLUSION:

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: Sang-Oh Lee, Robert A Brown, Seung H Kang, Rima C Abdel Massih, Raymund R Razonable
• Journal: Transplantation (Transplantation) Vol. 92 Issue 6 Pg. 690-6 (Sep 27 2011) ISSN: 1534-6080 [Electronic] United States
• PMID: 21822168 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• TLR4 protein, human
• Toll-Like Receptor 4

Topics

• Adult
• Bacterial Infections (complications, genetics)
• Cohort Studies
• Female
• Follow-Up Studies
• Genetic Predisposition to Disease
• Gram-Negative Bacteria (metabolism)
• Homozygote
• Humans
• Immune System
• Lipopolysaccharides (metabolism)
• Liver Failure (complications, therapy)
• Liver Transplantation (methods)
• Male
• Middle Aged
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide
• Postoperative Complications
• Proportional Hazards Models
• Toll-Like Receptor 4 (genetics)