title: Association of TNF-alpha promoter polymorphisms with the outcomes of hepatitis B virus infection in Chinese Han population.
abstract: Host genetic factors and environment factors including hepatitis B virus (HBV) genotypes are widely studied for the different outcomes of HBV infection. Recent studies suggest that tumour necrosis factor-alpha (TNF-alpha) plays a pivotal role in the viral clearance and host immune response to HBV, and the capacity for TNF-alpha production in individuals is influenced by a major genetic component. In this study, we aimed to explore whether the single-nucleotide polymorphisms (SNPs) of TNF-alpha promoter are associated with the outcomes of HBV infection in the Chinese Han population. One hundred and forty-three spontaneously recovered HBV subjects and 196 chronic hepatitis B patients were recruited in this case-control study in the Beijing area of China. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and sequence-specific primer-PCR (SSP-PCR) were used to detect the SNPs of five sites in the TNF-alpha promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in two groups were analysed by EPI and EH programs. The presence of the -238GG genotype was significantly correlated with persistence of HBV infection (OR = 4.08, P = 0.02), and -857TT genotype appeared in relation to the spontaneous clearance of HBV (OR = 0.47, P = 0.03). Frequency of haplotype GGCCT (-238/-308/-857/-863/-1031) in the chronic HB group was significantly lower than that in spontaneously recovered group (P = 0.03), and frequencies of haplotypes GGCAT and GGTAT in the chronic HB group were significantly higher than those in the spontaneously recovered group (P = 0.0001, P = 0.0004). In conclusion, TNF-alpha promoter polymorphisms are independently associated with different outcomes of HBV infection.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: T
authors.initials: T
authors.lastname: Du
authors.forename: X-H
authors.initials: XH
authors.lastname: Guo
authors.forename: X-L
authors.initials: XL
authors.lastname: Zhu
authors.forename: J-H
authors.initials: JH
authors.lastname: Li
authors.forename: L-P
authors.initials: LP
authors.lastname: Lu
authors.forename: J-R
authors.initials: JR
authors.lastname: Gao
authors.forename: C-Y
authors.initials: CY
authors.lastname: Gou
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006509:Hepatitis B / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D014409:Tumor Necrosis Factor-alpha