Effect of Functional Interleukin-10 Polymorphism on Pegylated Interferon-α Plus Ribavirin Therapy Response in Chronic Hepatitis C Virus Patients Infected With 3a Genotype in Pakistani Population
Hepatitis Monthly: June 01, 2013, 13 (6); e10274
June 8, 2013
Article Type: Letter
January 14, 2013
April 8, 2013
M S, Anjum
N U S S. Effect of Functional Interleukin-10 Polymorphism on Pegylated Interferon-α Plus Ribavirin Therapy Response in Chronic Hepatitis C Virus Patients Infected With 3a Genotype in Pakistani Population,
Hepacivirus; Interleukin-10; Polymorphism, Genetic; Pakistan
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Pakistan is a low socio economic country having more than 10 million people infected with hepatitis C Virus (HCV) with a major genotype of 3a (GT 3a) (
1). Due to high rate of resistance to standard Interferon plus Ribavirin therapy, it is highly needed to identify new marker for response prediction to therapy. Interleukin 10 (IL-10) is a key member of Cytokine, which regulates Th1/Th2 Cytokine balance, a major part of immune system against infection ( 2). IL-10 production varies inter individually based on functional polymorphism (-1082 G/A, -819 C/T and -592 C/A) in its promoter region. Previously we have shown that IL-10 polymorphic variants play important role in HCV susceptibility/prevention ( 2). Recently we conducted a study to analyze the impact of functionally important IL-10 polymorphism on outcomes of standard Interferon-α plus Ribavirin therapy. The results of current study strengthen previous findings that IL-10 polymorphism effect disease susceptibility in Pakistan ( 2- 4). Our results showed that high IL-10 producing -1082 GG genotype (P = 0.02; OR = 0.4; 95% CI = 0.2-0.8) and GTA haplotype (P = 0.03; OR = 0.55; 95% CI = 0.3-1) were significantly higher in HCV patients as compared to healthy subjects, while IL-10 -1082 GA genotype (P = 0.03; OR = 1.95; 95% CI = 1.1-3.4) showed protective effect against HCV infection. The current data failed to show any significant corelation between IL-10 polymorphism inheritance and standard therapy response in HCV patients. Age and pretreatment viral load are the parameters which influence therapy response; Patients with sustained virological response (SVR) were younger and had lower pretreatment HCV RNA levels. No gender-based statistical difference was found between chronic hepatitis C patients who achieved SVR or failed to respond. To our knowledge this is the first report from Pakistan to evaluate the role of IL-10 polymorphism on the outcomes of standard antiviral therapy. We are unable to find any corelation between IL-10 polymorphic variants and interferon therapy outcomes, may be due to small number of subjects. This study is a preliminary and is on small scale. We believe that our effort may stimulate some additional personal genetic makeup based studies on larger scale using these and new multi-locus analysis approaches for a deeper analysis of the epistatic interaction of the pro- and anti -inflammatory molecules toward hepatitis C progression. Better understanding of genetic factors that have effect on hepatitis C progression and pathogeneses will provide scientific basis for the development of new immunomodulatory treatments for chronic hepatitis C patients and will also help health care workers about the standard therapy effectiveness.
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