A tumor necrosis factor-alpha-inducible promoter variant of interferon-gamma accelerates CD4+ T cell depletion in human immunodeficiency virus-1-infected individuals

J Infect Dis. 2003 Jul 15;188(2):228-31. doi: 10.1086/376455. Epub 2003 Jul 9.

Abstract

A polymorphism, -179G/T, in the promoter of the interferon (IFN)-gamma gene (IFNG) confers differential tumor necrosis factor-alpha (TNF-alpha) inducibility to the IFNG promoter. The rarer allele, -179T, but not -179G, is inducible by TNF-alpha. We investigated the effects of IFNG -179G/T on AIDS pathogenesis. In 298 African American human immunodeficiency virus (HIV)-1 seroconverters, the IFNG -179G/T genotype was associated with accelerated progression to CD4 <200 and AIDS-1993, a finding suggesting that IFNG -179T is a risk factor for AIDS progression, as measured by CD4 cell count. It is possible that increased IFN-gamma production induced by TNF-alpha when -179T is present causes CD4 cell depletion by apoptosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alleles
  • Apoptosis
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology*
  • Disease Progression
  • Female
  • Gene Expression Regulation / drug effects
  • Genotype
  • HIV Infections / genetics*
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • HIV-1
  • Humans
  • Interferon-gamma / genetics*
  • Interferon-gamma / immunology*
  • Male
  • Polymorphism, Genetic / genetics
  • Promoter Regions, Genetic / genetics*
  • Proportional Hazards Models
  • Survival Analysis
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Tumor Necrosis Factor-alpha
  • Interferon-gamma