Abstract
The adaptive immune system plays an important role in response to interferon plus ribavirin treatment of hepatitis C virus (HCV) infection. Cytokines play a significant role in the adaptive immune system. The production of cytokines may be regulated by single nucleotide polymorphisms (SNPs). This study was designed to examine the correlation of some important SNPs of cytokines with interferon plus ribavirin treatment of HCV infection in the Pakistani population. We followed 140 chronic HCV-infected patients in our study. All of these patients had completed their planned course of interferon plus ribavirin treatment. We also considered 120 healthy subjects as controls. The detection of interleukin-18 (IL-18) SNPs was performed by tetra-primers amplification-refectory mutation system polymerase chain reaction, while for genotyping of osteopontin (OPN), transforming growth factor beta (TGFβ), and N-acetylgalactosaminyltransferase 8 (GALNT8) SNPs, allele-specific polymerase chain reaction was performed. The distribution of the IL-18 −607AA genotype varied significantly between healthy control and patient groups. Its distribution was significantly high in healthy subjects than HCV patients (p=0.031), signifying its potential involvement in the natural clearance of HCV infection. The occurrence of the −607AA genotype of IL-18 was also significantly higher in the sustained virological group (SVR) than in the nonresponder (NR) group (p=0.046), highlighting its protective involvement in the treatment outcome of chronic HCV infection. The frequency of the OPN −442TT genotype was higher in the SVR group than in the NR group (p=0.034), indicating a significant possible role of this genotype in therapy for HCV infection. No important association was found between TGFβ and GALNT8 genotypes and the natural clearance and treatment response of HCV infection. IL-18 −607AA and OPN −442TT genotypes can be used as positive predictive markers of interferon plus ribavirin treatment of HCV infection in the Pakistani population.
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