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    Effects of the Chemokine Receptor 5 (CCR5)-Delta32 Mutation on Hepatitis C Virus-Specific Immune Responses and Liver Tissue Pathology in HCV Infected Patients
    (Kowsar Publ, 2014) Yilmaz, Abdulkerim; Alagozlu, Hakan; Özdemir, Öztürk; Arici, Sema
    Background: The specific antiviral T cells provide CC chemokine receptor 5 (CCR5) for the immune response during the hepatitis C virus (HCV) infection. Heterogenous and/or homozygous 32 base pair deletion in CCR5 gene (CCR5 432 bpdel) leads to reduced protein expression. Objectives: In the current case control study, we aimed to compare the histopathological findings of liver to the CCR5 432 bpdel mutation profiles, expression and some other clinical findings in patients with chronic HCV infection. Materials and Methods: Multiple Strip Assay reverse hybridisation and Real Time PCR techniques were used to determine the germline CCR5 mutations and immunohistochemical technique was used to evaluate the gene expression in targer tissue biopsies. Results: Target CCR5 WT/WT, WT/ Delta 32, and Delta 32/ Delta 32 genotypes were observed in 91.4%, 8.6% and 0.0% for HCV positive patients and 98.3%, 1.7% and 0.0% for control group respectively. The histologic activity index(HAI) was significantly lower(4.0 +/- 1.0) in the mutated group than the non-mutated group (5.7 +/- 1.0). Decreased fibrosis levels were detected in HCV positive mutated group. Conclusions: Results showed that CCR5 polymorphism was more frequent in HCV positive patients than in healthy population in Turkish population. Current results also showed that mutated CCR5 signalling pathway due to CCR5-Delta32 may potentially result in subtle reduction of HCV specifity to the drug responses due to the positive impact on liver inflammation, fibrosis levels and liver destruction in HCV infection.