A Study Of The Association Between Genetic Polymorphisms In TNF-α And The Change Extent Of Helper Cells Associated Cytokines In CHB Treated With IFN-α

Objective: To study the association between -238G/A and -308G/A polymorphisms of TNF-αgene promoter and the alterations in concentration of IL-2,IFN-γ,IL-4 and IL-10 secreted by CD4 T cell in PBMCs after interferon-αtreatment, trying to find the mechanism of chronic hepatitis B and the treatment strategy.Methods: Seventy-seven patients with chronic hepatitis B were subjected to a standard course of treatment with interferon-α. The genomic DNAs were extracted from PBMCs isolated prior to treatment starts. TNF-αgene segments were amplified by a Polymerase Chain Reaction with specific primer pairs. Following PCR, the amplification products were digested with the restriction enzyme, and the polymorphisms were detected by agarose gel electrophoresis. Sera IL-2, IFN-γ, IL-4 and IL-10 were quantified by ELISA. All the results were analyzed with SPSS (12.0) software.Results: (1)There were no significant differences in the distribution of the genotypic polymorphisms of TNF-α-238 and TNF-α-308 between responders and nonresponders which were treated with interferon-α(P>0.05) .(2)The pre-treatment levels of IL-2,IFN-γwere higher in responders than nonresponders (p<0.05), while the IL-10 was lower(p<0.05).there were no significant differences in IL-4 between the two groups(P>0.05).(3)The level of IFN-γwas higher in -308 G/A genetype than -308 G/G genetype (p<0.05),but IL-2,IL-4,IL-10 were no significant differences in 308 G/A genetype and -308G /G genetype (P>0.05). The levels of IL-2,IFN-γ,IL-4,IL-10 were no significant difference between -238 G/A genetype and -238 G/G genotype (P>0.05).(4)After six months treatment with interferon-α, the levels of IL-2,IFN-γwere higher than those from pre-treatment patients while the IL-4 and IL-10 decreased significantly after treatment (p<0.05) .The average change extent of IL-2,IFN-γ, IL-4 and IL-10 before and after treatment in the responders was significantly higher than in the nonresponders (p<0.05).(5)There were no significant differences in the average change levels of IL-2,IFN-γ, IL-4 and IL-10 before and after treatment with interferon-αin TNF-α-238G/G,G/A genetype and TNF-α-308 G/G,G/A genetype (P>0.05).Conclusion: (1) There is no relationship between the genotypic polymorphisms of TNF-α-238,-308 and the degree of response to interferon-αtherapy in patients with chronic Hepatitis B.(2) The degree of response to interferon-αtherapy correlated with the concentration of IL-2,IFN-γ,IL-10 from pretreatment PBMCs. The level of IL-2,IFN-γ,IL-10 in pretreated PBMCs can be used to predict the interferon-αtherapy.(3) TNF-α-308 G/A genetype correlated with the higher level of IFN-γ, but there is no association with IL-2,IL-4 and IL-10 . The level of IL-2, IFN-γ, IL-4 and IL-10 has no association with the genotypic polymorphisms of TNF-α-238.(4) The degree of response to interferon-αtherapy was related to the change level of IL-2, IFN-γ, IL-4 and IL-10 after treatment with Interferon-α.(5) The genotypic polymorphisms of TNF-α-238 and TNF-α-308 were not related to the change level of IL-2, IFN-γ, IL-4 and IL-10 after treatment with Interferon-α.