A tumor necrosis factor-α-inducible promoter variant of interferon-γ accelerates CD4+ t cell depletion in human immunodeficiency virus-1-infected individuals

Ping An; David Vlahov; Joseph B. Margolick; John Phair; Thomas R. O'Brien; James Lautenberger; Stephen J. O'Brien; Cheryl A. Winkler

doi:10.1086/376455

A tumor necrosis factor-α-inducible promoter variant of interferon-γ accelerates CD4⁺ t cell depletion in human immunodeficiency virus-1-infected individuals

Ping An, David Vlahov, Joseph B. Margolick, John Phair, Thomas R. O'Brien, James Lautenberger, Stephen J. O'Brien, Cheryl A. Winkler^*

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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 promoter. 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.

Original language	English (US)
Pages (from-to)	228-231
Number of pages	4
Journal	Journal of Infectious Diseases
Volume	188
Issue number	2
DOIs	https://doi.org/10.1086/376455
State	Published - Jul 15 2003

Funding

Received 18 November 2002; accepted 18 February 2003; electronically published 9 July 2003. Presented in part: 52nd Annual Meeting of American Society of Human Genetics, Baltimore, Maryland, 15–19 October 2002 (abstract 1136). Financial support: National Cancer Institute; National Institutes of Health (contract NO1-CO-124000). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. Reprints or correspondence: Dr. Cheryl Winkler, Bldg. 560, NCI-FCRDC, Frederick, MD 21702 ([email protected]).

ASJC Scopus subject areas

General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1086/376455

Cite this

@article{48cfd255043c47e1bdb3013c4a82d3ef,

title = "A tumor necrosis factor-α-inducible promoter variant of interferon-γ accelerates CD4+ t cell depletion in human immunodeficiency virus-1-infected individuals",

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 promoter. 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.",

author = "Ping An and David Vlahov and Margolick, {Joseph B.} and John Phair and O'Brien, {Thomas R.} and James Lautenberger and O'Brien, {Stephen J.} and Winkler, {Cheryl A.}",

note = "Funding Information: Received 18 November 2002; accepted 18 February 2003; electronically published 9 July 2003. Presented in part: 52nd Annual Meeting of American Society of Human Genetics, Baltimore, Maryland, 15–19 October 2002 (abstract 1136). Financial support: National Cancer Institute; National Institutes of Health (contract NO1-CO-124000). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. Reprints or correspondence: Dr. Cheryl Winkler, Bldg. 560, NCI-FCRDC, Frederick, MD 21702 ([email protected]).",

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AU - An, Ping

AU - Vlahov, David

AU - Margolick, Joseph B.

AU - Phair, John

AU - O'Brien, Thomas R.

AU - Lautenberger, James

AU - O'Brien, Stephen J.

AU - Winkler, Cheryl A.

N1 - Funding Information: Received 18 November 2002; accepted 18 February 2003; electronically published 9 July 2003. Presented in part: 52nd Annual Meeting of American Society of Human Genetics, Baltimore, Maryland, 15–19 October 2002 (abstract 1136). Financial support: National Cancer Institute; National Institutes of Health (contract NO1-CO-124000). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. Reprints or correspondence: Dr. Cheryl Winkler, Bldg. 560, NCI-FCRDC, Frederick, MD 21702 ([email protected]).

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N2 - 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 promoter. 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.

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