Identification Of Genetic Polymorphisms In Tumor Necrosis Factor-alpha Allele And Its Association With HBV Or HCV Infection In Chinese Han Population

Background: Some adult subjects can efficiently clarify the virus and soon recover through the acute self-limited infection phase, but around 5% (or 80%) of HBV-infected or HCV-infected subjects become the chronic infection. Since the host susceptibility and clinical outcome to HBV or HCV infections are not only attributed to the virological and immunological factors, but also predetermined by human genetic factor. Previous study has shown that the TNF- a can interfere HBV or HCV replication and clarify viruses in the liver of patients with chronic HBV or HCV infection. The TNF- a gene is located within the class III region of MHC complex between HLA-B and -DR sites. Polymorphisms in the promoter regions of TNF-alpha gene have been shown to influence TNF- aexpression, but little is known regard to the effect of polymorphism of TNF- allele on the pathogenesis and disease progression of HBV and HCV infection. The aim of this study is to address whether the polymorphisms in TNF-alpha promoter and coding regions influence the susceptibility and progression in Chinese Han patients with chronic HBV or HCV infection.Methods: The genomic DNA samples were purified from the whole peripheral blood of 232 HBV-infected patients, 71 HCV-infected patients and 103 healthy controls from Chinese Han ethnic group. All the individuals were randomly selected. The single nucleotide polymorphisms in TNF- a promoter or code regions at positions -238nt, -244nt, -308nt, +152nt, +1252nt were determined by using PCR- RFLP (restriction fragment length polymorphism) assay. The association of genetic polymorphisms with human susceptibility of HBV and HCV infection was identified with statistical analyses based on the clinical data of the HBV-infected or HCV-infected patients.Results (1) The distribution of mutant frequencies of -308 (G A) in TNF- a gene promoter region was 4.74% for HBV-infected patients, 9.15% for HCV-infected patients and 9.71% for healthy individuals, respectively. Statistical analysis showed there is a significant decrease of mutant frequency in HBV-infected patients (P<0.05). (2) The prevalence of thevariant at position -238nt (G ) was similar in HBV or HCV-infected patients and healthy group, which shown there is no statistical difference between the groups (P > 0.05) .(3) The mutations in TNF- a promoter and code region at the positions -244nt, +152nt, +1252nt were not found. The mutant distribution of the TNF- a promoter region at positions examined in this study was in good agreememt with Hardy-Weiberg equilibrium.Conclusion (1) Our data suggests that the matation polymorphism site (-308 nt) in TNF- a allele promoter region may be served as a genetic resistant factor against the hepatitis B virus infection, the detailed underlying mechanism needs to be further clarified. (2) No association was found between TNF- a promoter polymorphism at position -238nt and the disease progression of the patients with chronic HBV or HCV infection. (3) There is no linkage disequilibrium relationship between the -238nt and -308nt site based on the statistical analysis.