RGD Reference Report - HCV-related liver and lymphoproliferative diseases: association with polymorphisms of IL28B and TLR2. - Rat Genome Database

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HCV-related liver and lymphoproliferative diseases: association with polymorphisms of IL28B and TLR2.

Authors: De Re, Valli  De Zorzi, Mariangela  Caggiari, Laura  Lauletta, Gianfranco  Tornesello, Maria Lina  Fognani, Elisa  Miorin, Marta  Racanelli, Vito  Quartuccio, Luca  Gragnani, Laura  Russi, Sabino  Pavone, Fabio  Ghersetti, Michela  Costa, Elena Garlatti  Casarin, Pietro  Bomben, Riccardo  Mazzaro, Cesare  Basaglia, Giancarlo  Berretta, Massimiliano  Vaccher, Emanuela  Izzo, Francesco  Buonaguro, Franco Maria  De Vita, Salvatore  Zignego, Anna Linda  De Paoli, Paolo  Dolcetti, Riccardo 
Citation: De Re V, etal., Oncotarget. 2016 Jun 21;7(25):37487-37497. doi: 10.18632/oncotarget.9303.
RGD ID: 15090815
Pubmed: PMID:27183918   (View Abstract at PubMed)
PMCID: PMC5122326   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.9303   (Journal Full-text)

To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV-related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection. Analysis of TLR2-IL28B haplotypes showed an association of wild type haplotype with the lymphoproliferative diseases (OR 1.77, p = 0.029) and a slight increase in HCV viral load (HR 1.38, p = 0.054). Wild type haplotype (TLR2 ins/ins- IL28B C/C) was also found associated with older age in patients with an hepatic diseases (in CIR and in HCC p = 0.038 and p = 0.020, respectively) supporting an effect of innate immunity in the liver disease progression. TLR2 and IL28B polymorphisms in combination showed a role in the control of HCV viral load and different HCV disease progression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular carcinoma susceptibilityIAGP 15090815DNA:deletion:promoter:-196 to -174(human)RGD 
hepatocellular carcinoma susceptibilityISOTLR2 (Homo sapiens)15090815; 15090815DNA:deletion:promoter:-196 to -174(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr2  (toll-like receptor 2)

Genes (Mus musculus)
Tlr2  (toll-like receptor 2)

Genes (Homo sapiens)
TLR2  (toll like receptor 2)


Additional Information