An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus.
An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus.
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DOI：
10.1182/blood.v96.7.2562
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发表时间：
2000-10
期刊：
影响因子：
20.3
通讯作者：
Charles B. Foster;Thomas Lehrnbecher;Susan Samuels;Steven Stein;Femke Mol;Julie A. Metcalf;Kathy Wyvill;Seth M. Steinberg;Joseph Kovacs;Andrew Blauvelt;R. Yarchoan;S. J. Chanock
中科院分区：
文献类型：
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作者：
Charles B. Foster;Thomas Lehrnbecher;Susan Samuels;Steven Stein;Femke Mol;Julie A. Metcalf;Kathy Wyvill;Seth M. Steinberg;Joseph Kovacs;Andrew Blauvelt;R. Yarchoan;S. J. Chanock
卡波西肉瘤(KS)是一种血管增生性炎症性疾病，常见于感染人类免疫缺陷病毒(HIV)的患者。炎性细胞因子和生长因子促进KS的发生发展。由于生理上重要的细胞因子基因多态性调节宿主的炎症反应，我们研究了KS与5个致炎细胞因子基因编码白介素IL-1α、IL-1β、肿瘤坏死因子α、肿瘤坏死因子-β和IL-6以及在IL-1受体拮抗剂(IL1RN)中常见的调节基因多态之间的关系。我们还研究了基质衍生因子1和趋化因子受体5(Delta32)基因多态性在KS发生中的作用。该人群包括115名患有KS的艾滋病毒感染男性和126名死于艾滋病毒感染而没有KS的男性。仅观察到IL6启动子多态性(G-174C)与HIV感染男性KS易感性之间的强烈关联(P=0.0035)。IL 6等位基因G纯合子在KS患者中的表达高于等位基因C(P=0.0046)，而等位基因C的纯合子表达不足(P=0.0062)。大量的体外证据表明，IL-6参与了KS的发病机制。我们的结果表明，与基因表达改变相关的IL6启动子基因型是KS发生的危险因素。确定KS发生的遗传危险因素对预防和治疗具有重要的临床意义。
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-1alpha, IL-1beta, tumor necrosis factor (TNF) alpha, TNF-beta, 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 (Delta32) 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.