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

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

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  • 1Basic Research Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702, USA.


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.

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