An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus

C. B. Foster, T. Lehrnbecher, S. Samuels, S. Stein, F. Mol, J. A. Metcalf, K. Wyvill, S. M. Steinberg, J. Kovacs, A. Blauvelt, R. Yarchoan, S. J. Chanock

Research output: Contribution to journalArticle

Abstract

Kaposi sarcoma (KS) is an angioproliferative inflammatory condition that occurs commonly in patients infected with human immunodeficiency virus (HIV). Inflammatory cytokines and growth factors promote the development of KS. Because physiologically important cytokine polymorphisms modulate host inflammatory responses, we investigated the association between KS and common regulatory polymorphisms in 5 proinflammatory cytokine genes encoding interleukin (IL) IL-1α, IL-1β, tumor necrosis factor (TNF)α, TNF-β, and IL-6 and in the IL-1 receptor antagonist (IL1RN). We also examined the contribution of stromal-derived factor 1 and chemokine receptor 5 (Δ32) polymorphisms to KS development. The population consisted of 115 HIV-infected men with KS and 126 deceased HIV-infected men without KS. The only strong association was observed between an IL6 promoter polymorphism (G-174C) and susceptibility to KS in HIV-infected men (P = .0035). Homozygotes for IL6 allele G, associated with increased IL6 production, were overrepresented among patients with KS (P = .0046), whereas allele C homozygotes were underrepresented (P = .0062). Substantial in vitro evidence indicates that IL-6 contributes to the pathogenesis of KS. Our results show that IL6 promoter genotypes associated with altered gene expression are risk factors for development of KS. Identification of a genetic risk factor for development of KS has important clinical implications for prevention and therapy. (C) 2000 by The American Society of Hematology.

Original languageEnglish (US)
Pages (from-to)2562-2567
Number of pages6
JournalBlood
Volume96
Issue number7
StatePublished - Oct 1 2000
Externally publishedYes

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Kaposi's Sarcoma
Polymorphism
Viruses
Interleukin-6
HIV
Cytokines
Interleukin-1
Tumor Necrosis Factor-alpha
Gene encoding
Homozygote
Interleukin-1 Receptors
Chemokine Receptors
Interleukins
Gene expression
Intercellular Signaling Peptides and Proteins
Alleles
Genotype
Gene Expression

ASJC Scopus subject areas

  • Hematology

Cite this

Foster, C. B., Lehrnbecher, T., Samuels, S., Stein, S., Mol, F., Metcalf, J. A., ... Chanock, S. J. (2000). An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus. Blood, 96(7), 2562-2567.

An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus. / Foster, C. B.; Lehrnbecher, T.; Samuels, S.; Stein, S.; Mol, F.; Metcalf, J. A.; Wyvill, K.; Steinberg, S. M.; Kovacs, J.; Blauvelt, A.; Yarchoan, R.; Chanock, S. J.

In: Blood, Vol. 96, No. 7, 01.10.2000, p. 2562-2567.

Research output: Contribution to journalArticle

Foster, CB, Lehrnbecher, T, Samuels, S, Stein, S, Mol, F, Metcalf, JA, Wyvill, K, Steinberg, SM, Kovacs, J, Blauvelt, A, Yarchoan, R & Chanock, SJ 2000, 'An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus', Blood, vol. 96, no. 7, pp. 2562-2567.
Foster CB, Lehrnbecher T, Samuels S, Stein S, Mol F, Metcalf JA et al. An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus. Blood. 2000 Oct 1;96(7):2562-2567.
Foster, C. B. ; Lehrnbecher, T. ; Samuels, S. ; Stein, S. ; Mol, F. ; Metcalf, J. A. ; Wyvill, K. ; Steinberg, S. M. ; Kovacs, J. ; Blauvelt, A. ; Yarchoan, R. ; Chanock, S. J. / An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus. In: Blood. 2000 ; Vol. 96, No. 7. pp. 2562-2567.
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abstract = "Kaposi sarcoma (KS) is an angioproliferative inflammatory condition that occurs commonly in patients infected with human immunodeficiency virus (HIV). Inflammatory cytokines and growth factors promote the development of KS. Because physiologically important cytokine polymorphisms modulate host inflammatory responses, we investigated the association between KS and common regulatory polymorphisms in 5 proinflammatory cytokine genes encoding interleukin (IL) IL-1α, IL-1β, tumor necrosis factor (TNF)α, TNF-β, and IL-6 and in the IL-1 receptor antagonist (IL1RN). We also examined the contribution of stromal-derived factor 1 and chemokine receptor 5 (Δ32) polymorphisms to KS development. The population consisted of 115 HIV-infected men with KS and 126 deceased HIV-infected men without KS. The only strong association was observed between an IL6 promoter polymorphism (G-174C) and susceptibility to KS in HIV-infected men (P = .0035). Homozygotes for IL6 allele G, associated with increased IL6 production, were overrepresented among patients with KS (P = .0046), whereas allele C homozygotes were underrepresented (P = .0062). Substantial in vitro evidence indicates that IL-6 contributes to the pathogenesis of KS. Our results show that IL6 promoter genotypes associated with altered gene expression are risk factors for development of KS. Identification of a genetic risk factor for development of KS has important clinical implications for prevention and therapy. (C) 2000 by The American Society of Hematology.",
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