GENETIC BASIS OF SEVERE MALARIAL ANEMIA

严重疟疾贫血的遗传基础

• 批准号: 6651607
• 负责人: Douglas Jay Perkins
• 金额: $ 46.54万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651607
• 关键词: Africa; Plasmodium falciparum; anemia; clinical research; cytokine; gene expression; genetic polymorphism; genetic susceptibility; human subject; immunoregulation; infant human (0-1 year); interleukin 10; interleukin 12; longitudinal human study; malaria; medical complication; migration inhibition factor; nitric oxide; pathologic process; patient oriented research; preschool child (1-5); prostaglandin E; transforming growth factors; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): Children residing in holoendemic regions of malaria transmission, such as western Kenya, are at an increased risk for developing life-threatening complications due to severe malarial anemia (SMA). Our recent findings in this area illustrate that the highest rates of SMA-associated morbidity and mortality occur in children between birth and 2 years of age. Therefore, we will investigate the genetic and immunologic mechanisms of SMA in young children residing in Kisumu, Kenya. Since effective cell-mediated immunity is required for controlling malaria infection, we will focus on defining the role of cytokines [interleukin (IL )-12, tumor necrosis factor (TNF)-alpha, macrophage migration inhibitory factor (MIF), IL-10 and transforming growth factor (TGF)-beta1], and effector molecules [nitric oxide (NO) and prostaglandin (PG)-E2] in the immunopathogenesis of SMA. The goals of this proposal are: 1) to identify unique profiles of cytokine and effector molecule gene expression associated with the development and outcome of SMA, 2) to determine if polymorphisms in the cytokine and effector molecule genes lead to disequilibrium in the cytokine balance that affects the clinical course and outcome of SMA, and 3) to identify novel patterns of gene expression associated with the immunopathogenesis of SMA. The overall goal of this proposal is to identify the immunomodulatory genes, whose critical patterns of expression underlie disease susceptibility to SMA. Successful completion of this project, that takes into account the complex genetic, inflammatory, and clinical factors that promote malarial anemia, will offer important information for the future development and testing of malaria vaccine candidates.

描述（由申请人提供）：居住在肯尼亚西部疟疾传播的全部流行区域的儿童，由于严重的疟疾贫血（SMA）而导致危及生命的并发症的风险增加。我们最近在该领域的发现表明，与SMA相关的发病率和死亡率最高的发生率是出生到2岁之间的儿童。因此，我们将研究居住在肯尼亚Kisumu的幼儿中SMA的遗传和免疫学机制。 Since effective cell-mediated immunity is required for controlling malaria infection, we will focus on defining the role of cytokines [interleukin (IL )-12, tumor necrosis factor (TNF)-alpha, macrophage migration inhibitory factor (MIF), IL-10 and transforming growth factor (TGF)-beta1], and effector molecules [nitric oxide (NO) and 在SMA的免疫病作用中，前列腺素（Pg）-e2]。该提案的目标是：1）确定与SMA的发育和结果相关的细胞因子和效应分子基因表达的独特特征，2）确定在细胞因子和效应分子基因中的多态性是否导致细胞因子平衡中影响SMA和SMA的临床表现形式和3个基因的临床疗程和3）的基因的临床和结果。该提案的总体目标是确定免疫调节基因，其表达的批判性模式是疾病对SMA的敏感性。成功完成该项目，该项目考虑了促进疟疾贫血的复杂遗传，炎症和临床因素，将提供重要的 未来开发和测试疟疾疫苗候选者的信息。