Human Molecular Genetics Advance Access published online on August 5, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg262
© 2003 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
* To whom correspondence should be addressed. E-mail: hsleemd{at}snu.ac.kr.
The mechanisms underlying the resolution of hepatitis B virus (HBV) infection remain undetermined. Tumor necrosis factor-
Article
Association of TNF-
Promoter Polymorphisms With the Clearance of Hepatitis B Virus Infection
2 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-dong, Chongno-gu, Seoul 110-744, Korea
3 Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea
4 Department of Genetic Epidemiology, SNP Genetics, Inc., Seoul, Korea
Abstract 
(TNF-) 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- promotor polymorphisms are associated with the clearance of HBV infection. A total of 1,400 Korean subjects were enrolled in 2 different groups: "chronic carrier group" (CC; n=1,109), 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- 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- promoter alleles that were previously reported to be associated with higher plasma levels, i.e., the presence of the -308A allele (TNF--308A/G or A/A) or the absence of the -863A (TNF--863C/C) variant, were strongly associated with the resolution of HBV infection in three alternative analyzing models, i.e., TNF--308G>A (P=0.01) and TNF--863C>A (P=0.003-0.14), respectively. Haplotype analysis also revealed that TNF- 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- might be an important factor, which might explain the variable outcome of HBV infection.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Liu, E. J. Metter, L. Ferrucci, and S. M. Roth TNF promoter polymorphisms associated with muscle phenotypes in humans J Appl Physiol, September 1, 2008; 105(3): 859 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kleinrath, C. Gassner, P. Lackner, M. Thurnher, and R. Ramoner Interleukin-4 Promoter Polymorphisms: A Genetic Prognostic Factor for Survival in Metastatic Renal Cell Carcinoma J. Clin. Oncol., March 1, 2007; 25(7): 845 - 851. [Abstract] [Full Text] [PDF]
|
|