Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa

Virology Journal, Jan 2011

In order to examine whether variation in interleukin-10 promoter polymorphism would predict the likelihood of sustain response of chronic hepatitis B to treatment with interferon alfa (IFN-α), the inheritance of 3 biallelic polymorphisms in the IL-10 gene promoter in patients with 52 chronic hepatitis B were determined by polymerase chain reaction (PCR)-bared techniques, restriction enzyme digestion or direct sequencing. The relationship to the outcome of antiviral therapy for chronic HBV infection was studied in 24 patients who had a virologically sustained response(SR) and in 28 non-responder(NR) to interferon alfa-2b and several IL-10 variants were more frequent among SR compared with NR. Carriage of the -592A allele, -592A/A genotype and -1082/-1819/-592 ATA haplotype was associated with SR. Our findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of chronic hepatitis B to IFN-α therapy.

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Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa

Virology Journal Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa Shaoyang Wang 0 Dedong Huang 0 Shunlai Sun 0 Weimin Ma 0 Qin Zhen 0 0 Department of infectious diseases, the Fuzhou General Hospital , Fu Zhou, Fujian Province 350003 , China In order to examine whether variation in interleukin-10 promoter polymorphism would predict the likelihood of sustain response of chronic hepatitis B to treatment with interferon alfa (IFN-a), the inheritance of 3 biallelic polymorphisms in the IL-10 gene promoter in patients with 52 chronic hepatitis B were determined by polymerase chain reaction (PCR)-bared techniques, restriction enzyme digestion or direct sequencing. The relationship to the outcome of antiviral therapy for chronic HBV infection was studied in 24 patients who had a virologically sustained response(SR) and in 28 non-responder(NR) to interferon alfa-2b and several IL-10 variants were more frequent among SR compared with NR. Carriage of the -592A allele, -592A/A genotype and -1082/-1819/-592 ATA haplotype was associated with SR. Our findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of chronic hepatitis B to IFN-a therapy. - Introduction Hepatitis B is a worldwide disease and remains a significant etiology of chronic hepatitis, cirrhosis and hepatocellular carcinoma, especially in several areas of Asia and Africa[1]. It is estimated to affect over 350 million people worldwide, with a mortality of over 1.2 million deaths per year because of acute or chronic hepatitis B infection[2,3]. For active hepatitis B patients with detectable hepatitis B virus e antigen (HBeAg) or hepatitis B virus (HBV) DNA and elevated alanine aminotransferase (ALT) serum levels, treatment is often recommended. Six-month course of interferon alfa (IFN-a) therapy has been shown to induce a long-term sustained remission in 25% to 40% of chronic hepatitis B patients[1,4,5]. However, the question remains unresolved as to why only a certain percentage of patients respond to therapy. Hence, predictive factors determining therapeutic responses are focused by many investigations. Multivariate analyses have shown that the most important predictors of good response to IFN-atreatment include high ALT levels, low serum HBV DNA, female gender, and histological activity on liver biopsy in chronic HBV patients[6-8]. However, despite these studies of viral factors and clinical markers affecting treatment response, the role of the host genetic background was less well studied[9]. The role of cytokines and the cellular immune response in the pathogenesis and eradication of chronic HBV has been investigated. Several proinflammatory cytokines such as Th1 cytokines (including IL-2 and IFN-g) and TNF-a are believed to participate in elimination of HBV [8,10,11]. In contrast, IL-10 and IL-4, Th2 cytokine, act as potent inhibitors of Th1 effectors mechanisms[8,12-14]. There are some evidences that the capacity for cytokine production in individuals has a major genetic component [15]. This has been ascribed to polymorphisms within the regulatory regions or signal sequences of cytokine. Several polymorphic sites within the IL-10 gene promoter region have been described, including three bi-allelic polymorphisms at positions1082, 819, and 592 from the transcription start site. The IL-10819 T and C alleles were completely in linkage disequilibrium with the IL-10592A and C alleles, respectively. The592A allele was exclusively associated with the1082A allele. These result in three different haplotypes: GCC, ACC, and ATA[16]. It was reported that allelic variation in these polymorphisms may be associated with the disease progression of chronic HBV infection[17]. Heterogeneity in the promoter region of the IL-10 gene has been reported to have a role in determining the initial and sustained response of chronic hepatitis C to IFN-atherapy[18]. However, there are differences in the immunopathogenesis of HBV and HCV infection[19], it is necessary to investigate whether IL-10 gene promoter polymorphisms could serve as a candidate prediction of response to IFN-atherapy in chronic HBV infection. To prove this hypothesis, we examined the inheritance of the 3 biallelic polymorphisms in patients with chronic HBV and the association of these polymorphisms with response to IFN-a. For HBV patients, it is very important to predict the response to antiviral therapy, especially for IFN-a therapy, given the many displeasing side effects associated with this medical regimen and the high cost of therapy. Patients and methods Patients We retrospectively enrolled 52 Chinese Han patients with chronic hepatitis B from our outpatients clinics at Fuzhou general hospital, between February 2007 and December 2008. There were 28 non-responders (NR) to IFN treatment with a mean age of 32 years and 24 sustained responders (SR) with a mean age of 35 years. (...truncated)


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Shaoyang Wang, Dedong Huang, Shunlai Sun, Weimin Ma, Qin Zhen. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis B to interferon alfa, Virology Journal, 2011, pp. 28, 8, DOI: 10.1186/1743-422X-8-28