PMID- 12915457
OWN - NLM
STAT- MEDLINE
DCOM- 20040519
LR  - 20081121
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 12
IP  - 19
DP  - 2003 Oct 1
TI  - Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B 
      virus infection.
PG  - 2541-6
AB  - 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.
FAU - Kim, Yoon Jun
AU  - Kim YJ
AD  - Department of Internal Medicine and Liver Research Institute, Seoul National 
      University College of Medicine, 28 Yungun-dong, Chongno-gu, Seoul 110-744, Korea.
FAU - Lee, Hyo-Suk
AU  - Lee HS
FAU - Yoon, Jung-Hwan
AU  - Yoon JH
FAU - Kim, Chung Yong
AU  - Kim CY
FAU - Park, Myoung Hee
AU  - Park MH
FAU - Kim, Lyoung Hyo
AU  - Kim LH
FAU - Park, Byung Lae
AU  - Park BL
FAU - Shin, Hyoung Doo
AU  - Shin HD
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030805
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Hepatitis B Core Antigens)
RN  - 0 (Hepatitis B Surface Antigens)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 6
MH  - Female
MH  - Genetic Variation
MH  - Haplotypes
MH  - Hepatitis B Core Antigens/genetics
MH  - Hepatitis B Surface Antigens/genetics
MH  - Hepatitis B virus
MH  - Hepatitis B, Chronic/*genetics
MH  - Heterozygote
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Odds Ratio
MH  - *Polymorphism, Genetic
MH  - *Promoter Regions, Genetic
MH  - Retrospective Studies
MH  - Sex Ratio
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 2003/08/14 05:00
MHDA- 2004/05/20 05:00
CRDT- 2003/08/14 05:00
PHST- 2003/08/14 05:00 [pubmed]
PHST- 2004/05/20 05:00 [medline]
PHST- 2003/08/14 05:00 [entrez]
AID - ddg262 [pii]
AID - 10.1093/hmg/ddg262 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2003 Oct 1;12(19):2541-6. doi: 10.1093/hmg/ddg262. Epub 2003 Aug 
      5.