SOCS3 mRNA expression and polymorphisms as pretreatment predictor of response to HCV genotype 3a IFN-based treatment.
OBJECTIVE
Suppressor 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.


METHODS
This 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).


RESULTS
Gene 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.


CONCLUSIONS
The 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.
Department of Immunology, University of Health Sciences Lahore, Khayaban-e-Jamia Punjab, Lahore, Pakistan.
Rabia
R
Aslam
Department of Physiology & Cell Biology, University of Health Sciences Lahore, Khayaban-e-Jamia Punjab, Lahore, Pakistan ; Allied Health Sciences, University of Health Sciences Lahore, Lahore, Pakistan.
Syed Mohsin
SM
Raza
Department of Immunology, University of Health Sciences Lahore, Khayaban-e-Jamia Punjab, Lahore, Pakistan.
Humeira
H
Naeemi
Department of Immunology, University of Health Sciences Lahore, Khayaban-e-Jamia Punjab, Lahore, Pakistan.
Bushra
B
Mubarak
Department of Immunology, University of Health Sciences Lahore, Khayaban-e-Jamia Punjab, Lahore, Pakistan.
Nadeem
N
Afzal
Department of Physiology & Cell Biology, University of Health Sciences Lahore, Khayaban-e-Jamia Punjab, Lahore, Pakistan ; Department of Immunology, University of Health Sciences Lahore, Khayaban-e-Jamia Punjab, Lahore, Pakistan.
Saba
S
Khaliq
HCV; Interferon therapy; Relapsers; Responders; SOCS3