NICHD Small Grants Programs

NICHD 小额赠款计划

• 批准号: 6707003
• 负责人: Felix O Aikhionbare
• 金额: $ 7.1万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6707003
• 关键词: HIV infections; clinical research; disease /disorder proneness /risk; embryo /fetus tissue /cell culture; gene mutation; genetic markers; genetic polymorphism; histocompatibility gene; human fetus tissue; human genetic material tag; human tissue; immunogenetics; immunopathology; linkage disequilibriums; major histocompatibility complex; molecular cloning; nucleic acid sequence; pediatric AIDS; polymerase chain reaction; single strand conformation polymorphism; statistics /biometry; vertical transmission

DESCRIPTION (provided by applicant): Perinatal transmission accounts for more than 90 percent of HIV-infection in children. A thorough understanding of the molecular and genetics mechanisms of the host immune gene response (such as chemokines, cytokines, HLA polymorphisms) effecting the pathogens and transmission consequences of host-HIV-1 interactions is essential to all aspects of public health for diagnostic, transmission, and prevention strategies. This study is designed to understand the mutational role of HLA-G gene that make HIV-1 infected women more (or less likely) to transmit virus to her infant. HLA-G is non-classical class 1 MHC gene and it is highly expressed in extravillous cytotrophoblast at the maternal fetal interface. Specific aim: To further examine the potential role (s) of the mutation in HLA-G exon 2, which was previously associated to reduced risk in perinatal transmission (Aikhionbare, AIDS 2001,15: 2196-8) and any mutation(s) in HLA-G untranslated region in DNA samples obtained from both Project RETRO-C1, 01 BP 1712, 10 Abidjan Cote d'Ivoire and Perinatal AIDS Collaborative Transmission Study (PACTS), for possibly increase or decrease in the susceptibility of a neonate to HIV-1- perinatal transmission. Approach: DNA samples will be obtained from HIV-1-infected and uninfected mother-child pairs followed as part of Project RETRO-C1, 01 BP 1712, 10 Abidjan Cote d'Ivoire and Perinatal AIDS Collaborative Transmission Study will be screened by the following techniques: WAVETM Nucleic Acid Fragment Analysis, allele-specific polymerase chain reaction (PCR), single strand conformational polymorphism (SSCP), followed by DNA cloning/sequencing. Molecular data from this study will be subjected to Fisher's exact test, Maximum likelihood, Linked disequilibrum parameter, Odd ratio, Relative risk analysis to groups value. Results will furnish new insights into the basic mechanisms of the viral pathogenesis in AIDS, especially the contribution of certain host genetic factors to HIV-1 perinatal infection.

描述（由申请人提供）：围产期传播占儿童艾滋病毒感染的90%以上。全面了解宿主免疫基因反应的分子和遗传学机制（如趋化因子、细胞因子、HLA多态性）对宿主- hiv -1相互作用的病原体和传播后果的影响，对公共卫生诊断、传播和预防策略的各个方面至关重要。这项研究旨在了解HLA-G基因的突变作用，使HIV-1感染的妇女更容易（或更不可能）将病毒传播给她的婴儿。HLA-G是一种非经典的1类MHC基因，它在母胎界面的胞外滋养细胞中高度表达。具体目的：进一步研究HLA-G外显子2突变的潜在作用，该突变先前与围产期传播风险降低有关（Aikhionbare, AIDS 2001,15）；2196-8)以及来自Project retroc - c1、01 BP 1712、10 Abidjan Cote d' ivire和围产期艾滋病合作传播研究（PACTS）的DNA样本中HLA-G非翻译区的任何突变，可能增加或减少新生儿对HIV-1-围产期传播的易感性。方法：将从hiv -1感染和未感染的母婴对中获得DNA样本，作为项目retroc - c1, 01 BP 1712, 10阿比让科特迪瓦和围产期艾滋病协同传播研究的一部分，将通过以下技术进行筛选：WAVETM核酸片段分析，等位基因特异性聚合酶链反应（PCR），单链构象多态性（SSCP），然后进行DNA克隆/测序。本研究的分子数据将进行Fisher精确检验、最大似然、关联不平衡参数、奇数比、相对风险分析。这些结果将为艾滋病病毒发病的基本机制，特别是某些宿主遗传因素对HIV-1围产期感染的贡献提供新的见解。