RGD Reference Report - Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection. - Rat Genome Database

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Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection.

Authors: Kim, Yoon Jun  Lee, Hyo-Suk  Yoon, Jung-Hwan  Kim, Chung Yong  Park, Myoung Hee  Kim, Lyoung Hyo  Park, Byung Lae  Shin, Hyoung Doo 
Citation: Kim YJ, etal., Hum Mol Genet. 2003 Oct 1;12(19):2541-6. doi: 10.1093/hmg/ddg262. Epub 2003 Aug 5.
RGD ID: 14995438
Pubmed: PMID:12915457   (View Abstract at PubMed)
DOI: DOI:10.1093/hmg/ddg262   (Journal Full-text)

The mechanisms underlying the resolution of hepatitis B virus (HBV) infection remain undetermined. Tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in host immune response to HBV, and the capacity for cytokine production in individuals has a major genetic component. The aim of this study was to examine whether TNF-alpha promotor polymorphisms are associated with the clearance of HBV infection. A total of 1400 Korean subjects were enrolled in two different groups: 'chronic carrier group' (CC; n=1109), who were repeatedly hepatitis B surface antigen (HBsAg)-positive, and 'subjects who spontaneously recovered' (SR; n=291), who were HBsAg-negative with antibodies to HBsAg and hepatitis B core antigen. TNF-alpha promoter polymorphisms at positions -1031T>C, -863C>A, -857C>T, -376G>A, -308G>A, -238G>A and -163G>A were determined and the genotype distributions of the CC and SR groups were compared. The TNF-alpha promoter alleles that were previously reported to be associated with higher plasma levels, i.e. the presence of the -308A allele (TNF-alpha-308A/G or A/A) or the absence of the -863A (TNF-alpha-863C/C) variant, were strongly associated with the resolution of HBV infection in three alternative analyzing models, i.e. TNF-alpha-308G>A (P=0.01) and TNF-alpha-863C>A (P=0.003-0.14), respectively. Haplotype analysis also revealed that TNF-alpha haplotype 1 [-1031T; -863C; -857C; -308G; -238G; -163G] and haplotype 2 [-1031C; -863A; -857C; -308G; -238G; -163G] were significantly associated with HBV clearance, showing protective antibody production and persistent HBV infection, respectively (P=0.003-0.02). Our findings imply that variations in the genes governing the levels of constitutive and inducible TNF-alpha might be an important factor, which might explain the variable outcome of HBV infection.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TNFHumanhepatitis B severityIAGP DNA:SNPs:promoter:-863C>A and -308A>G (human)RGD 
TnfRathepatitis B severityISOTNF (Homo sapiens)DNA:SNPs:promoter:-863C>A and -308A>G (human)RGD 
TnfMousehepatitis B severityISOTNF (Homo sapiens)DNA:SNPs:promoter:-863C>A and -308A>G (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
TNF  (tumor necrosis factor)


Additional Information