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.

Association of tumor necrosis factor-α gene polymorphism with osteoarticular tuberculosis prognosis in a Hebei population

“…There have been many reports on the association of TNF-α-308, -238, and -863 with different diseases, such as hepatitis B virus infection (Du et al, 2006;Basturk et al, 2008) and breast cancer (Yang et al, 2011). In our study, we combined the three SNPs and the haplotype association analysis of TNF-α SNPs (-308/-238/-863) showed that the TNF-α AGA haplotype was present at a higher frequency in the OA-TB patients (12.1%) than in the healthy volunteers (3.5%), indicating that it was a risk factor for OA-TB (OR = 4.201, 95%CI = 1.80-9.91, P = 0.010).…”

Association of the IFNAR1-17470 and IL-10-592 cytokine variants with susceptibility to chronic hepatitis B viral infections in a Chinese population

“…The base replacement of G to A at site -308 leads to sequence variants in its promoter region. Several studies have reported conflicting results regarding the effect of the TNF-α-308 sequence variants on chronic hepatitis B (CHB) viral infections (Höhler et al, 1998;Du et al, 2006;Basturk et al, 2008).…”

Relationship between -238A/G and -308A/G polymorphisms in the promoter region of TNF-α and susceptibility to gout in the Chinese Han male population

“…The important biological effects of TNF-α and the location of TNF-α (within a region of chromosome 6) have prompted studies on the relationship between TNF-α polymorphisms and diseases. Studies have found that the TNF-α-238A/G polymorphism is closely associated with many autoimmune diseases, such as Hepatitis B [15], SLE [16], coronary heart disease complicated with diabetes mellitus [17], and aplastic anemia [18]. TNF-α-238A is the disease susceptibility allele and -238G is the protective allele.…”