GENETIC EPIDEMIOLOGY OF AIDS AND THE ROLE OF CHEMOKINE GENES

一系列体内和体外研究已经确定了一些 细胞基因在艾滋病毒和人类免疫缺陷病毒的传染性中发挥关键作用 艾滋病在感染者中的疾病进展。一个这样的团体 包括趋化因子。趋化因子是与肝素结合的小分子 趋化单核细胞、中性粒细胞和T细胞的蛋白质，以及 充当炎症的中介物。在过去的一年里，它已经表现出来了 而这些趋化因子配体的受体有一半被用作 HIV的共同受体，为病毒进入提供了对接端口 细胞。我们目前正在对所有32名人类进行突变分析 一系列临床明确的患者队列中的趋化因子基因。 五个队列由几个协作单位组成， 集体由大约3000名个人组成，他们可以被分配到 三大临床类型之一：暴露、未感染、快速 进步者和长期幸存者。我们正在设计过程中 用于人类不同区域的聚合酶链式反应引物 趋化因子基因。这些基因正在使用单链进行筛选 144人小组的构象多态(SSCP)程序 根据种族可分为六个亚类的个人 和临床倾向。任何SSCP变体都明显出现在 队列之间的不同频率将被排序和转换 转化为限制性片段长度多态性分析用于筛查 数量更多的个体。目前，潜在的 在几个基因中已经发现了信息性的多态。其中之一 这些基因，SDF-1，已经被广泛地描述并似乎 延缓高加索人的疾病进展。(见项目Z01 BC 10264-01 Lgd)。

A series of in vivo and in vitro studies has identified a number of cellular genes that play pivotal roles in the infectivity of HIV and in the disease progression of AIDS in infected individuals. One such group of genes includes the chemokines. Chemokines are small heparin-binding proteins that chemoattract monocytes, neutrophils, and T-cells, and serve as mediators of inflammation. It has been shown in the past year and one-half that the receptors for these chemokine ligands are used as co-receptors for HIV, providing the virus a docking port for entry into cells. We are currently carrying out a mutation analysis of all 32 human chemokine genes in a series of clinically well-defined patient cohorts. Five cohorts were assembled by several collaborating units and collectively consist of about 3000 individuals who can be assigned to one of three major clinical categories: exposed, uninfected; rapid progressors; and long-term survivors. We are in the process of designing polymerase chain reaction primers for different regions of all human chemokine genes. The genes are being screened using the single strand conformational polymorphism (SSCP) procedure on a panel of 144 individuals that are divisible into six subcategories based upon race and clinical disposition. Any SSCP variants appearing at appreciably different frequencies between cohorts will be sequenced and converted into a restriction fragment length polymorphism assay for screening larger numbers of individuals. At the present time, potentially informative polymorphisms have been identified in several genes. One of these genes, SDF-1, has been extensively characterized and appears to delay disease progression in Caucasians. (See Project Z01 BC 10264-01 LGD).