Polymorphisms of Toll-like receptors 2 and 4 in chronically infected hepatitis C patients from north-east Croatia
- 230 Downloads
Chronic infection with hepatitis C virus (HCV) is caused by an inadequate immune response. Experimental data suggest that the impaired activation of Toll-like receptors (TLRs) 2 and 4 contributes to chronic infection. We assessed the distribution of three single-nucleotide polymorphisms (SNPs) in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly/Thr399Ile) genes in individuals from north-east Croatia and their effect on the outcome of antiviral therapy. The study consisted of 60 chronically infected patients and 40 healthy subjects. TLR polymorphisms were determined by the PCR-based melting curve analysis. HCV genotyping was performed using the Linear Array Hepatitis C Virus Genotyping Test. Thirty-three patients were treated with standard interferon and ribavirin therapy, and their viral load was evaluated at weeks 28 and 53 after the beginning of therapy. The majority of chronic infections were caused by genotype 1 (77%), followed by genotypes 3 (15%) and 4 (7%). Patients with genotype 1 had higher viral loads than patients infected with other genotypes (P = 0.0428). Healthy individuals and patients with chronic infection had similar frequencies of TLR2-Arg753Gln and TLR4-Asp299Gly/Thr399Ile SNPs. Heterozygous and homozygous TLR4-Asp299Gly/Thr399Ile polymorphisms correlated with higher viral loads and delayed responses to antiviral therapy. We have provided the first evidence that TLR4 polymorphisms influence the success of antiviral therapy in our region. This suggests that therapeutic strategies should be adjusted not only according to HCV genotype but also to individual TLR polymorphism(s).
KeywordsViral Load Antiviral Therapy High Viral Load Thr399Ile Polymorphism Monte Carlo Simulation Step
This study was supported by the Institute of Public Health of Osijek-Baranja County. The authors declare that they have no conflict of interest. The authors also greatly appreciate the help received from Dr. Marcela Čović for revision of the article.
- 6.Kosanović ML, Knežević J (2006) Epiemiological Characteristics of Individuals Tested for Hepatitis C at Zagreb Institute of Public Health [In Croatian]. HČJZ 2:1–3Google Scholar
- 16.Schröder NW, Schumann RR (2005) Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease. Lacent Infect Dis 5:156–164Google Scholar
- 22.Radstake TRDJ, Franke B, Hanssen S, Netea MG, Welsing P, Barrera P, Joosten LAB, van Riel PLCM, van den Berg WB (2004) The Toll-like receptor 4 Asp299Gly functional variant is associated with decreased rheumatoid arthritis disease susceptibility but does not influence diseade severity and/or outcome. Arthritis Rheum. doi: 10.1002/art.20114 Google Scholar
- 24.Orozco G, Morales S, González-Gay MÁ, González Rugeles CI, Ramírez Qintero G, Martín J (2005) Toll-like receptor 4 Asp299Gly polymorphism and reumatoid arthritis: a replicative study in three different populations. Inmunología 24:205–207Google Scholar
- 30.Tićac B, Rukavina T (2007) Seological Diagnosis Of Hepatitis C Viral Infection—Situation In Primorsko-goranska County (in Croatian). Medicina 43:123–131Google Scholar