Genetic Modulation of Sickle Cell Anemia

镰状细胞性贫血的基因调控

• 批准号: 7231659
• 负责人: Martin H. Steinberg
• 金额: $ 3.08万
• 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/7231659
• 关键词: Accounting; Affect; African American; Anticoagulation; Area; Arts; Biological; Biology; Blood Vessels; Blood coagulation; Brazil; Candidate Disease Gene; Cell Communication; Cell Proliferation; Cells; Class; Clinical; Clinical Research; Complementary DNA; Complex; DNA Databases; Data Set; Decision Making; Disease; Endothelial Cells; Funding; Gene Expression; Gene-Modified; Genes; Genetic; Genetic Polymorphism; Genotype; Hereditary Disease; Heterogeneity; Human; Inflammation; Interleukin-1; Leukocytes; Link; Metabolism; Methods; Nitric Oxide; Numbers; Patients; Pattern; Phenotype; Population; Proteins; Research Infrastructure; Research Personnel; Sampling; Sickle Cell Anemia; Single Nucleotide Polymorphism; Site; Stimulus; Therapeutic; Training; United States National Institutes of Health; Vasomotor; Work; genetic association; migration; novel; parent grant; patient registry; prognostic; repository

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 - 表型关联研究可能会提供重要的预后信息，并指导遗传疾病的治疗决策。镰状细胞贫血的表型，一种原型的孟德尔单基因疾病，是众所周知的异质性。多样性可能是由于许多修饰基因的作用和相互作用而产生的。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 - 细胞相互作用。我们的新颖观察结果将候选基因中的多态性与非裔美国人镰状细胞贫血的表型联系起来，并由父母赠款资助，需要将其扩展到另一个人群并得到证实。巴西巴伊亚萨尔瓦多（Salvador）为确认和其他研究提供了理想的地点。大量的镰状细胞疾病患者居住在该地区，并且存在可重新聚焦在遗传关联研究上的临床和研究基础设施。这项工作将使我们更加靠近预言和治疗，同时在萨尔瓦多进行现代遗传研究的能力。我们的主要目标是：1）从巴西巴比亚萨尔瓦多的镰状细胞病患者的数据库和DNA样品存储库开发镰状细胞疾病。 2）巴伊亚州巴西患者的候选基因中的单核苷酸多态性（SNP）。这些结果将与我们在非裔美国人中的发现进行比较，这些结果提供了有关地理不同人群中调节基因的相似性和差异的信息。 3）培训巴西研究人员在最新的大型复杂数据集的分析方法中培训研究者，同时继续完善在预后有用的交互式网络中使用多态性的方法。我们的结果还将使巴西研究人员与我们合作在新的NIH NIH细胞疾病临床研究网络中与我们合作。