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

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 h...

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Bibliographic Details
Published in:Transplant infectious disease 2013-04, Vol.15 (2), p.111-119
Main Authors: Lee, S.-O., Brown, R.A., Razonable, R.R.
Format: Article
Language:English
Subjects:
Adult
Aged
chronic hepatitis C
cirrhosis
Female
graft failure
Graft Rejection - mortality
HCV
Hepacivirus - genetics
Hepacivirus - immunology
Hepatitis C virus
Hepatitis C, Chronic - genetics
Hepatitis C, Chronic - immunology
Hepatitis C, Chronic - mortality
Humans
Liver Transplantation
Male
Middle Aged
mortality
Multivariate Analysis
polymorphism
Polymorphism, Single Nucleotide
Risk Factors
Toll-like receptor 3
Toll-Like Receptor 3 - genetics
Toll-Like Receptor 3 - immunology
Transplantation, Homologous
Treatment Outcome
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Summary: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.
ISSN:1398-2273
1399-3062
DOI:10.1111/tid.12033