IDENTIFICATION OF CANDIDATE GENE POLYMORPHISMS THAT INFLUENCE PROGRESSION TO AIDS

影响艾滋病进展的候选基因多态性的鉴定

• 批准号: 6101083
• 负责人: C WINKLER
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6101083
• 关键词: AIDS; African American; HIV infections; caucasian American; clinical research; cytokine receptors; gene frequency; genetic mapping; genetic polymorphism; genetic susceptibility; human genetic material tag; human immunodeficiency virus 1; human subject; pathologic process; racial /ethnic difference; transcription factor

The variable character of the HIV-1 epidemicamong world populations suggests that racial distribution of polymorphisms for relevantgenes may be important. Polymorphisms in chemokine receptors have been shown to have aprofound effect on both infection and the rate ofprogression to AIDS in Caucasians. Of thethree protective alleles reported, CCR5-delta32,CCR2-64I, andSDF1-3'A, only CCR2-64I iscommon in African-Americans or native Africans,but it appears to be less protective than inCaucasians. We have identified severalpolymorphisms in HIV-1 candidate genes that occurwith high frequency in African-Americans.Preliminary analyses suggest that there may be complex interactions between chemokine receptorgenes that increase susceptibility to diseaseprogression in a cohort of African Americans. Weare also identifying polymorphisms in bothCaucasians and African-Americans that occur inhost genes encoding proteins, includingtranscriptional factors, that are involved inpost-entry events. Several of these polymorphismsare now being screened for their effects oninfection and progression in the two racial groups.Identification of Candidate Gene Polymorphisms that Influence Progression to AIDS

HIV-1流行病的不同特征 世界人口表明，种族分布 相关基因的多态性可能很重要。多态性 在趋化因子受体中已被证明具有深远的作用 对白种人的感染率和艾滋病进展率的影响。 在报告的三个保护性等位基因中，CCR5-delta32、CCR2-64I、 和SDF1-3'A，只有CCR2-64I在非裔美国人或 非洲本土人，但它的保护作用似乎不如非洲人 在白种人中。我们已经鉴定出 HIV-1 的几种多态性 出现频率高的候选基因 非裔美国人。初步分析表明，可能有 趋化因子受体基因之间复杂的相互作用 增加非洲人群疾病进展的易感性 美国人。我们还鉴定了多态性 白人和非洲裔美国人都发生在宿主基因中 编码蛋白质，包括转录因子， 涉及进入后事件。其中一些多态性是 目前正在筛选它们对感染和进展的影响 两个种族群体候选基因的鉴定 影响艾滋病进展的多态性