TNF-α polymorphisms affect persistence and progression of HBV infection.
Adult
Alleles
Asian People
/ genetics
Case-Control Studies
DNA, Viral
/ blood
Disease Progression
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
Hepatitis B virus
/ genetics
Hepatitis B, Chronic
/ genetics
Homozygote
Humans
Male
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Tumor Necrosis Factor-alpha
/ genetics
chronic hepatitis B
host factor
mass spectrometry
single-nucleotide polymorphism
tumor necrosis factor-α
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
27
03
2019
revised:
30
07
2019
accepted:
04
08
2019
pubmed:
24
8
2019
medline:
23
6
2020
entrez:
24
8
2019
Statut:
ppublish
Résumé
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. A total of 231 patients with CHB constituted the study group and 100 healthy volunteers-the local control group. TNF-α -1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A were genotyped using MALDI-TOF mass spectrometry. TNF-α -1031C and -863A alleles were observed more frequently in CHB group than in healthy controls. Carriers of TNF-α -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-α variants and liver fibrosis were found. This study indicates that TNF-α -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.
Sections du résumé
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-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.
METHODS
A total of 231 patients with CHB constituted the study group and 100 healthy volunteers-the local control group. TNF-α -1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A were genotyped using MALDI-TOF mass spectrometry.
RESULTS
TNF-α -1031C and -863A alleles were observed more frequently in CHB group than in healthy controls. Carriers of TNF-α -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-α variants and liver fibrosis were found.
CONCLUSION
This study indicates that TNF-α -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.
Identifiants
pubmed: 31441603
doi: 10.1002/mgg3.935
pmc: PMC6785446
doi:
Substances chimiques
DNA, Viral
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e00935Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
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