Interleukin-4 polymorphisms and response to combination therapy in Egyptian chronic hepatitis C patients
ABSTRACT In hepatitis C infection, the production of inappropriate cytokines levels may contribute to viral persistence and may affect the response to antiviral therapy. We investigate the effect of IL4 C-590T and C-33T polymorphisms on the response to combination therapy with interferon and ribavirin in chronic HCV patients. These single nucleotide polymorphisms were determined by PCR-RFLP in 235 responder and 210 non-responder to combination therapy. The IL4-590 T/T and -33 T/T genotypes were associated with resistance to the therapy (p<0.001, p=0.001 respectively). Haplotypes T(-590) T(-33) and T(-590) C(-33) were associated with a higher risk in non-responder patients than the responders (p<0.001 for each) while frequency of haplotype C(-590) C(-33) (with all wild alleles) was significantly higher in responders as compared to non-responders (p<0.001). These results suggest that inheritance of the IL4 polymorphisms may be associated with resistance to combined antiviral therapy in Egyptian HCV patients.
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ABSTRACT: Objective: Dual PEGylated interferon-(PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population. Methods: Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. Results: IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNF(-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. Conclusions: IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
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ABSTRACT: OBJECTIVE: The aim of this meta-analysis is to evaluate the associations between functional polymorphisms in the interleukin-4 (IL4) gene and individuals' responses to hepatitis B vaccine and their susceptibility to hepatitis B virus (HBV) infection. METHODS: A literature search on articles published before December 1st, 2012 was conducted in PubMed, Embase, Web of Science and China BioMedicine (CBM) databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using the STATA 12.0 software. RESULTS: Eight studies were eligible for inclusion in this meta-analysis, including five cross-sectional studies on individual's response to hepatitis B vaccine and three case-control studies on HBV infection risk. The meta-analysis results showed that the T allele of rs2243250, the T allele of rs2070874, and the C allele of rs2227284 in IL4 gene were associated with high responses to hepatitis B vaccine. Further subgroup analysis by ethnicity showed that there was a significant association between IL4 genetic polymorphisms and an individual's responses to hepatitis B vaccine among Asian populations, but similar association was not found among Caucasian populations. However, there was no evidence indicating a correlation between IL4 genetic polymorphism and susceptibility to HBV infection. CONCLUSION: Our current meta-analysis suggests that rs2243250, rs2070874 and rs2227284 polymorphisms in IL4 gene may play an important role in determining the response to hepatitis B vaccine, especially among Asian populations. However, further studies are still needed to evaluate the associations between IL4 genetic polymorphisms and HBV infection risk.Gene 05/2013; 525(1). DOI:10.1016/j.gene.2013.04.065 · 2.08 Impact Factor
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ABSTRACT: Interleukin-4 (IL-4) is a pleiotropic cytokine that plays an important role in the immune system. Emerging evidences have shown that the common polymorphism (-590C/T; rs2243250 C>T) in the IL-4 gene may play an important role in the development of various liver diseases, but individually published studies revealed inconclusive results. This meta-analysis aims to derive a more precise estimation of the association between the IL-4 -590C/T polymorphism and susceptibility to liver disease. A literature search of PubMed, Embase, Web of Science and China BioMedicine databases was conducted on articles published before January 1st, 2013. Crude odds ratio with 95% confidence intervals were calculated to assess the strength of this association. Ten case-control studies were assessed with a total 1,140 patients and 1,649 healthy controls. The meta-analysis results indicated that the IL-4 -590T polymorphism might increase the risks of hepatitis B (HBV) and hepatitis C (HCV) infections. Further subgroup analyses showed significant associations between the IL-4 -590T polymorphism and increased risks of liver diseases among Caucasian populations, but similar associations were not found among Asian populations. Univariate and multivariate meta-regression analyses showed that differences in ethnicity and clinical subtype are the major sources of heterogeneity. No publication bias was detected in this meta-analysis. In conclusion, the current meta-analysis indicates that the IL-4 -590T polymorphism may play an important role in increasing HBV and HCV infection risks, especially among Caucasian populations.DNA and cell biology 06/2013; DOI:10.1089/dna.2013.2020 · 1.99 Impact Factor