Abstract
AimSuppressor of Cytokine Signaling 3 (SOCS3) gene belongs to SOCS family as one of the negative regulators of cytokine signaling and IFN response that function via the JAK-STAT pathway in antiviral response. SOCS3 expression and genetic polymorphism influences the pathogenesis and outcome of antiviral treatment in hepatitis C virus (HCV) infected patients. This study was designed for analysis of SOCS3 gene expression and polymorphism in Pakistani HCV patients.MethodsThis descriptive study was conducted on 250 diagnosed HCV genotype 3a infected subjects. The study population was divided into two major groups on the basis of therapeutic response i.e. sustained virological response (SVR) and non-responders/relapsers (NR). SOCS3 gene mRNA expression analysis was done by using Real time PCR technique, whereas ARMS PCR technique was used for analysis of SOCS3 gene polymorphisms i.e. 8464 A/C (rs12952093), −4874 A/G (rs4969170) and −1383 A/G, (rs4969168).ResultsGene expression analysis of SOCS3 showed that there was statistically significant increase of 2.275-fold and 3.72-fold in relative gene expression for SVR and NR as compared to normal healthy samples (p < 0.001). The distribution of rs4969168, rs4969170 and rs12952093 genotype frequencies between SVR versus NR group were not statistically significant, only the allelic frequency of rs4969170 was statistically significant (p ≤ 0.0001) with therapeutic response.ConclusionThe gene expression analysis of SOCS3 showed a clear difference in mRNA expression of SOCS3 as a possible indicator of therapeutic response rather than polymorphism of SOCS3 gene in our studied population.
Highlights
Cytokines including interleukins, interferons (IFNs i.e. IFN-α, IFN-β, and IFN-ω) and hemopoietins activate a potent positive feedback mechanism which produces high concentrations of IFNs locally after viral infection
Standard therapy against Hepatitis C virus (HCV) is a combination of immune modulator plus an antiviral agent [Pegylated interferon α (PEGIFN-α) and guanosine analog ribavirin], which predicts only a 50 % sustained virologic response (SVR; if HCV RNA remain undetectable at 6 months post treatment completion), depending upon HCV infected genotype (Tsubota et al 2011)
Out of these Suppressor of Cytokine Signaling 3 (SOCS3) polymorphisms AA genotype of rs4969170 is strongly associated with antiviral therapy in HCV patients that might be associated with high expression of hepatic SOCS3 (Persico et al 2008; Kim et al 2009)
Summary
Patients were excluded if they were positive for HBV or any other known viral infection, any type of liver diseases, malignancy i.e. HCC and others These patients were divided into two groups depending upon the treatment response i.e. Sustained virological response (SVR) and non-responders/relapse (NR). SOCS3 and STAT3 gene expression analysis To evaluate the effect of SOCS3 and STAT3 gene expression in HCV infected patients with different therapeutic response, total RNA was extracted from the blood sample of HCV patients and normal (healthy) volunteers followed by gene expression analysis. Due to problems in sample collection from all the patients at different time intervals, the RNA used for the Real Time PCR analysis consists of samples taken before start of therapy (later on designated as SVR or NR group) and from patients who already had a relapse of disease after completion of combination therapy. All the data analysis was performed by IBM SPSS ver. 21 while p value
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