GENETIC EPIDEMIOLOGY OF AIDS AND THE ROLE OF CHEMOKINE GENES

一系列的体内和体外研究已经确定了一些 细胞基因在艾滋病毒的感染性中起关键作用， 艾滋病在受感染者中的疾病进展。一个这样的组 包括趋化因子。趋化因子是小的肝素结合 化学吸引单核细胞、中性粒细胞和T细胞的蛋白质，以及 作为炎症介质。在过去的一年里， 这些趋化因子配体的受体的一半被用作 艾滋病毒的辅助受体，为病毒提供一个进入的对接端口， 细胞我们目前正在对所有32名人类 在一系列临床明确定义的患者队列中检测趋化因子基因。 几个合作单位组成了五个小组， 总共由大约3000人组成，他们可以被分配到 三种主要临床类别之一：暴露的，未感染的;快速的 长期生存者;长期生存者。我们正在设计 针对所有人的不同区域的聚合酶链反应引物 趋化因子基因这些基因是用单链DNA 构象多态性（SSCP）程序对一组144 根据种族可分为六个亚类的个体 和临床处置。任何SSCP变异出现在 将对队列之间的不同频率进行排序和转换 限制性片段长度多态性分析用于筛选 更多的个人。目前，潜在 已经在几个基因中鉴定了信息多态性。之一 这些基因，SDF-1，已经被广泛表征， 延缓高加索人的疾病进展。(See项目Z 01 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).