RGD Reference Report - The toll-like receptor 2 (TLR2) -196 to -174 del/ins polymorphism affects viral loads and susceptibility to hepatocellular carcinoma in chronic hepatitis C.

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The toll-like receptor 2 (TLR2) -196 to -174 del/ins polymorphism affects viral loads and susceptibility to hepatocellular carcinoma in chronic hepatitis C.
Authors:	Nischalke, Hans-Dieter Coenen, Martin Berger, Cordula Aldenhoff, Katharina Müller, Tobias Berg, Thomas Krämer, Benjamin Körner, Christian Odenthal, Margarete Schulze, Falko Grünhage, Frank Nattermann, Jacob Sauerbruch, Tilman Spengler, Ulrich
Citation:	Nischalke HD, etal., Int J Cancer. 2012 Mar 15;130(6):1470-5. doi: 10.1002/ijc.26143. Epub 2011 Jun 18.
RGD ID:	15090813
Pubmed:	PMID:21500195 (View Abstract at PubMed)
DOI:	DOI:10.1002/ijc.26143 (Journal Full-text)
Chronic hepatitis C virus (HCV) infection is a major risk factor for hepatocellular carcinoma (HCC). HCV proteins core and NS3 can bind to toll-like receptor 2 (TLR2) and trigger inflammatory responses. Polymorphisms in the TLR2 gene predispose to various forms of malignancy but have not been studied in HCV-associated HCC. Here, we investigated whether single nucleotide polymorphisms (SNPs), rs4696480, rs5743708, rs5743704 and the -196 to -174 del/ins polymorphism of the TLR2 gene affect the risk for HCC in chronic hepatitis C. The study involved 189 and 192 HCV genotype 1 infected patients with and without HCC, respectively, as well as 347 healthy controls. TLR2 alleles were determined by hybridization probe assays and allele-specific short fragment polymerase chain reaction on a LightCycler system. All TLR2 polymorphisms matched the Hardy-Weinberg equilibrium in each study group. Although TLR2 SNPs showed no effect, the frequency of the TLR2 -196 to -174 del allele was significantly higher in patients with HCV-associated HCC (22.5%) than in HCV-infected patients without HCC (15.6%, p = 0.016) and healthy controls (15.3%, p = 0.003). HCV-infected carriers of a TLR2 -196 to -174 del allele had significantly higher HCV viral loads than TLR2 -196 to -174 ins/ins homozygous patients (p = 0.031). Finally, in carriers of the TLR2 -196 to -174 del allele, stimulation of monocytes resulted in significantly lower TLR2 expression levels and interleukin-8 (IL-8) induction than in individuals with the TLR2 -196 to -174 ins/ins genotype (p < 0.05). Our data suggest the TLR2 -196 to -174 del allele to affect HCV viral loads and to increase the risk for HCC in HCV genotype1-infected patients.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
TLR2	Human	hepatocellular carcinoma	susceptibility	IAGP		associated with Hepatitis C more ...	RGD
Tlr2	Rat	hepatocellular carcinoma	susceptibility	ISO	TLR2 (Homo sapiens)	associated with Hepatitis C more ...	RGD
Tlr2	Mouse	hepatocellular carcinoma	susceptibility	ISO	TLR2 (Homo sapiens)	associated with Hepatitis C more ...	RGD

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Genes (Rattus norvegicus)

Tlr2 (toll-like receptor 2)

Genes (Mus musculus)

Tlr2 (toll-like receptor 2)

Genes (Homo sapiens)

TLR2 (toll like receptor 2)

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The toll-like receptor 2 (TLR2) -196 to -174 del/ins polymorphism affects viral loads and susceptibility to hepatocellular carcinoma in chronic hepatitis C.