A Tumor Necrosis Factor-α-Inducible Promoter Variant of Interferon-γ Accelerates CD4+ T Cell Depletion in Human Immunodeficiency Virus-1-Infected Individuals
P An, D Vlahov, JB Margolick, J Phair… - The Journal of …, 2003 - academic.oup.com
P An, D Vlahov, JB Margolick, J Phair, TR O'Brien, J Lautenberger, SJ O'Brien, CA Winkler
The Journal of infectious diseases, 2003•academic.oup.comAbstract A polymorphism,—179G/T, in the promoter of the interferon (IFN)-γ gene (IFNG)
confers differential tumor necrosis factor-α (TNF-α) inducibility to the IFNG= romoter. The
rarer allele,− 179T, but not− 179G, is inducible by TNF-α. 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 …
confers differential tumor necrosis factor-α (TNF-α) inducibility to the IFNG= romoter. The
rarer allele,− 179T, but not− 179G, is inducible by TNF-α. 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 …
Abstract
A polymorphism,—179G/T, in the promoter of the interferon (IFN)-γ gene (IFNG) confers differential tumor necrosis factor-α (TNF-α) inducibility to the IFNG =romoter. The rarer allele, −179T, but not −179G, is inducible by TNF-α.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-γ production induced by TNF-α when −179T is present causes CD4 cell depletion by apoptosis.
Oxford University Press