Association between a functional polymorphism in Toll-like receptor 3 and chronic hepatitis C in liver transplant recipients.

Abstract

BACKGROUND:

Toll-like receptor 3 (TLR3) is implicated in the pathogenesis of viral diseases owing to its ability to recognize viral double-stranded RNA. We hypothesized that single nucleotide polymorphism (SNP) in TLR3 gene that impairs the function of the protein-receptor influences the outcome of hepatitis C virus (HCV) infection after liver transplantation.

METHODS:

The clinical characteristics of 611 liver recipients (HCV-infected: n = 153, non-HCV-infected: n = 458) were assessed to investigate the impact of TLR3 L412F SNP on transplant outcomes.

RESULTS:

TLR3 L412F is common, and it was significantly more prevalent among the HCV-infected cohort (57.5% vs. 45.2%, P = 0.008). In a multivariate analysis, TLR3 L412F was significantly associated with chronic hepatitis C (odds ratio: 1.73, 95% confidence interval [CI]: 1.13-2.65, P = 0.01). In an analysis that compared HCV-infected patients with wild-type versus TLR3 L412F, a marginally higher rate of allograft failure and mortality was observed in the TLR3 L412F group (44.3% vs. 30.8%, P = 0.09). However, in a multivariate analysis, only donor age was significantly associated with allograft failure and mortality (relative risk: 1.04, 95% CI: 1.007-1.06, P = 0.02).

CONCLUSION:

TLR3 L412F is significantly common in HCV-infected liver recipients, and may be associated with worse outcomes. However, larger studies are needed to determine its significant association with allograft failure and mortality after liver transplantation for chronic hepatitis C.

• Authors: S-O Lee, R A Brown, R R Razonable
• Journal: Transplant infectious disease : an official journal of the Transplantation Society (Transpl Infect Dis) Vol. 15 Issue 2 Pg. 111-9 (Apr 2013) ISSN: 1399-3062 [Electronic] Denmark
• PMID: 23240626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 John Wiley & Sons A/S.

Chemical References

• Toll-Like Receptor 3

Topics

• Adult
• Aged
• Female
• Graft Rejection (mortality)
• Hepacivirus (genetics, immunology)
• Hepatitis C, Chronic (genetics, immunology, mortality)
• Humans
• Liver Transplantation
• Male
• Middle Aged
• Multivariate Analysis
• Polymorphism, Single Nucleotide
• Risk Factors
• Toll-Like Receptor 3 (genetics, immunology)
• Transplantation, Homologous
• Treatment Outcome