title: A tumor necrosis factor-alpha-inducible promoter variant of interferon-gamma accelerates CD4+ T cell depletion in human immunodeficiency virus-1-infected individuals.
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.
authors.affiliation: Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: David
authors.initials: D
authors.lastname: Vlahov
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.forename: John
authors.initials: J
authors.lastname: Phair
authors.forename: Thomas R
authors.initials: TR
authors.lastname: O'Brien
authors.forename: James
authors.initials: J
authors.lastname: Lautenberger
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Brien
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
mesh_terms: D000328:Adult; D000483:Alleles; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016016:Proportional Hazards Models; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma