Genetic Modulation of Sickle Cell Anemia

镰状细胞性贫血的基因调控

• 批准号: 7070296
• 负责人: Martin H. Steinberg
• 金额: $ 3.76万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7070296
• 关键词: clinical research; genes; genetics; phenotype; sickle cell anemia

DESCRIPTION (provided by applicant): Genotype-phenotype association studies may provide important prognostic information and guide therapeutic decision making in genetic disease. The phenotype of sickle cell anemia, a prototypic Mendelian single gene disorder, is notoriously heterogeneous. The diversity is likely to result from the actions and interactions of many modifying genes. Candidate disease modulating genes may regulate oxidative biology, nitric oxide metabolism, vascular function, inflammation and cell-cell interaction. Our novel observations linking polymorphisms in candidate genes with phenotypes of sickle cell anemia in African Americans and funded by the parent grant need to be expanded to another population and confirmed. Salvador, Bahia, Brazil provides an ideal site for confirmatory and additional studies. A large number of sickle cell disease patients reside in the area and a clinical and research infrastructure exists that can be refocused on genetic association studies. This work will move us closer toward applying our observations prognostically and therapeutically, while building the capacity for modern genetic studies in Salvador. Our prime objectives are: 1) developing a sickle cell disease patient registry, database and DNA sample repository of sickle cell disease patients from Salvador Bahia, Brazil. 2) genotyping single nucleotide polymorphisms (SNPs) in candidate genes in Brazilian patients in Bahia. These results will be compared with our findings in African Americans providing information on the similarities and differences in modulating genes in geographically distinct populations. 3) training Brazilian investigators in state-of-the-art methods of analysis of large complex data sets while continuing to refine methods for using polymorphisms in prognostically useful interactive networks. Our results will also prepare Brazilian investigators to collaborate with us in a new NIH Sickle Cell Disease Clinical Research Network.

描述（由申请人提供）：基因型-表型关联研究可以提供重要的预后信息并指导遗传病的治疗决策。镰状细胞性贫血是一种典型的孟德尔单基因疾病，其表型具有明显的异质性。这种多样性可能是由许多修饰基因的作用和相互作用造成的。候选疾病调节基因可能调节氧化生物学、一氧化氮代谢、血管功能、炎症和细胞间相互作用。我们的新观察结果将候选基因的多态性与非裔美国人的镰状细胞性贫血表型联系起来，并由父母资助，需要扩展到其他人群并得到证实。巴西巴伊亚州萨尔瓦多为验证性和额外研究提供了理想的场所。该地区居住着大量镰状细胞病患者，并且拥有可以重新专注于遗传关联研究的临床和研究基础设施。这项工作将使我们更接近于将我们的观察结果应用于预后和治疗，同时建设萨尔瓦多现代遗传学研究的能力。我们的主要目标是：1) 开发巴西萨尔瓦多巴伊亚镰状细胞病患者的镰状细胞病患者登记、数据库和 DNA 样本库。 2) 对巴伊亚巴西患者候选基因中的单核苷酸多态性 (SNP) 进行基因分型。这些结果将与我们在非裔美国人中的发现进行比较，提供有关不同地理人群中调节基因的相似性和差异的信息。 3）对巴西研究人员进行大型复杂数据集分析最先进方法的培训，同时继续完善在预测有用的交互式网络中使用多态性的方法。我们的研究结果还将帮助巴西研究人员与我们在新的 NIH 镰状细胞病临床研究网络中进行合作。