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

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 IL6promoter 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 thatIL6 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.

Cytokine IL‐1 beta but not IL‐1 alpha promoter polymorphism is associated with Alzheimer disease in a population from the Canary Islands, Spain

“…No further explanations can we drawn from this case-control study. As it has been previously described in other populations, again we found a strong association between AD and the E4 allele of the APOE gene in this study based on a Canarian population [24].…”

Genetic architecture of acne vulgaris

“…79 SNPs in the IL-6 gene are associated with multiple inflammatory conditions such as multiple sclerosis, 80 coronary artery disease, 81 Kaposi sarcoma. 82 Three case-control studies explored association signals in IL-1a and IL-6 in acne vulgaris ( Table 6). The single nucleotide polymorphism +4845(G>T) 75 and À889 C/T 83,84 in IL-1a and -572 G/C 84 of IL-6 correlated with the severity of the inflammatory acne vulgaris.…”

Genetic variation and hematopoietic stem cell transplantation: expansion of the paradigm

“…cystic fibrosis) or acquired, stressed states (e.g. immunosuppression and HIV infection) (16)(17)(18)(19)(20). SNPs can also modify or modulate pharmacological response to therapy (e.g.…”