TLR3 gene polymorphisms and liver disease manifestations in chronic hepatitis C

• Published in: Journal of medical virology Vol. 81; no. 7; pp. 1204 - 1211
• Main Authors: Askar, Eva, Bregadze, Rusudan, Mertens, Jasmin, Schweyer, Stefan, Rosenberger, Albert, Ramadori, Giuliano, Mihm, Sabine
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2009; Wiley
• Subjects: Adult; Biological and medical sciences; Exons; Female; Fundamental and applied biological sciences. Psychology; Genotype; HCV genotypes; Hepacivirus - genetics; Hepacivirus - isolation & purification; hepatitis C virus (HCV); Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - pathology; Human viral diseases; Humans; Infectious diseases; L412F; Male; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Mutation, Missense; Point Mutation; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; single nucleotide polymorphism (SNP); T-976A; Toll-like receptor (TLR); Toll-Like Receptor 3 - genetics; Viral diseases; Virology; hepatitis C virus (HCV); Toll like receptor 3; Genotype; Hepatic disease; Toll like receptor; T-976A; Infection; Virus; Gene; Toll-like receptor (TLR); Viral disease; single nucleotide polymorphism (SNP); Digestive diseases; HCV genotypes; L412F; Single nucleotide polymorphism; Flaviviridae; Hepatitis C virus; Hepacivirus; Viral hepatitis C
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.21491

Phenotypes of liver disease due to chronic hepatitis C virus (HCV) infection show a wide range of variations in terms of histological manifestations and the clinical outcome. Sensing of viral double-stranded RNA (dsRNA) by Toll-like receptor 3 (TLR3) is likely involved in early pathogen detection and the host response to viral infection. This study analyzed epidemiological and clinical data from a total of 137 patients with chronic HCV infection with regard to two polymorphic positions within the TLR3 gene: rs5743305 (T/A) is located within the promoter region and might affect transcriptional activity, rs3775291 (C/T) is a non-synonymous single nucleotide polymorphism (SNP) located within exon 4 and the variant receptor has been shown to be functionally impaired. TLR3 promoter and the exon 4 variations were not found to be associated with TLR3 gene expression in peripheral blood mononuclear cells (PBMCs). In the liver, however, a tendency of higher TLR3 gene expression was found for exon 4 TT genotypes. Both variations were not found to be associated with clinical parameters of chronic disease. On the other hand, an analysis of the TLR3 exon 4 genotype distribution with respect to HCV subtype revealed an absence of TT genotype among HCV subtype 1a infected individuals. This study thus failed to reveal any association of the two SNPs under investigation with clinical parameters of chronic hepatitis C. However, data argue for a functional relevance of the exon 4 SNP in terms of conferring a different susceptibility towards HCV subtype infection. J. Med. Virol. 81:1204-1211, 2009.