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TNF-? polymorphisms affect persistence and progression of HBV infection.

ABSTRACT: BACKGROUND:Hepatitis B virus (HBV) infections are a major threat worldwide. Disease progression and outcome is diverse and depends on host genetic background. Recently, a high rate of HBV reactivation in individuals receiving tumor necrosis factor-? (TNF-?) antagonists showed the importance of this cytokine in HBV infection control. Here, we investigated the influence of TNF-? promoter polymorphisms on susceptibility to chronic HBV infection (CHB), liver injury progression and outcomes. METHODS:A total of 231 patients with CHB constituted the study group and 100 healthy volunteers-the local control group. TNF-? -1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A were genotyped using MALDI-TOF mass spectrometry. RESULTS:TNF-? -1031C and -863A alleles were observed more frequently in CHB group than in healthy controls. Carriers of TNF-? -1031C and -863A variant alleles had lower baseline levels of serum HBV DNA and lower liver necroinflammatory activity than dominant homozygotes. A -857CT genotype predisposed to higher necroinflammatory activity. No associations between TNF-? variants and liver fibrosis were found. CONCLUSION:This study indicates that TNF-? -863A and -1031C alleles are associated with increased susceptibility to CHB in individuals from northern Poland. The same variants determine the course of CHB, lowering viremia and reducing necroinflammatory activity of the liver.

SUBMITTER: Woziwodzka A

PROVIDER: S-EPMC6785446 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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TNF-α polymorphisms affect persistence and progression of HBV infection.

Woziwodzka Anna A Rybicka Magda M Sznarkowska Alicja A Romanowski Tomasz T Dręczewski Marcin M Stalke Piotr P Bielawski Krzysztof Piotr KP

Molecular genetics & genomic medicine 20190823 10

<h4>Background</h4>Hepatitis B virus (HBV) infections are a major threat worldwide. Disease progression and outcome is diverse and depends on host genetic background. Recently, a high rate of HBV reactivation in individuals receiving tumor necrosis factor-α (TNF-α) antagonists showed the importance of this cytokine in HBV infection control. Here, we investigated the influence of TNF-α promoter polymorphisms on susceptibility to chronic HBV infection (CHB), liver injury progression and outcomes.< ...[more]

PMID: 31441603

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Project description:BackgroundApolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G) is a potent host defense factor, which interferes with HIV-1 and HBV. Our study had three objectives, to screen a population of HIV-1 infected and uninfected patients in Burkina Faso for HBV, to screen the population for APOBEC3G variants rs6001417, rs8177832, and rs35228531 previously described, and to analyze the effect of these three variants and their haplotypes on HIV-1/HBV co-infection in Burkina Faso.MethodsHBV detection was performed on samples from HIV-1 infected and uninfected subjects using rapid detection tests and real-time PCR. APOBEC3 genotyping was done by the TaqMan allelic discrimination method. Fisher Exact test, Odds ratio (OR), confidence intervals (CI) at 95 %, Linkage disequilibrium (LD) summary statistics and haplotype frequencies were calculated.ResultsThe prevalence of HBV was 56.7 % among HIV-1 positive patients of our study while it was about 12.8 % among HIV-1 seronegative subjects. Genotype E was the genotype of HBV present in our hepatitis B positive samples. Minor allele frequencies of rs6001417, rs8177832, and rs35228531 were higher in seronegative subjects. The T minor allele of variant rs35228531 was protective against HIV-1/HBV co-infection with OR = 0.61, 95 % CI (0.42-0.90), p = 0.013. There was also an association between the GGT haplotype and protection against HIV-1/HBV co-infection, OR = 0.57, 95 % CI (0.33-0.99), p = 0.050. The other haplotypes present in the population were not statistically significant. There minor allele T of the rs35228531 was protective against HIV mono-infection OR = 0.53, 95 % CI (0.3-0.93), P = 0.030. But there was no effect of protection against HBV mono-infection.ConclusionAPOBEC3G through its variants rs6001417, rs8177832, and rs35228531, in this study interferes with HIV-1/HBV co-infection could be due the HIV-1 mono-infection in a population from Burkina Faso.

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TNF-? polymorphisms affect persistence and progression of HBV infection.

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TNF-α polymorphisms affect persistence and progression of HBV infection.

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