Variation in Severity of Sickle Cell Disease among the Yorubas

约鲁巴人镰状细胞病严重程度的差异

基本信息

批准号：
8495443
负责人：
RIchard Stanley Cooper
金额：
$ 5.31万
依托单位：
LOYOLA UNIVERSITY CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8495443
关键词：
Africa African Caring Chicago Clinical Clinical Data Clinical Research Collaborations Complement Country DNA Data Databases Developed Countries Developing Countries Development Disease Disease Management Ethnic Origin Fetal Hemoglobin Genes Genetic Genetic Variation Genomics Genotype Grant Hemoglobinopathies High Prevalence Hospitals Hypertension Institution Jamaica Knowledge Laboratories Lead Life Cycle Stages Life Expectancy Link Mainstreaming Malaria Measures Medical Meta-Analysis Modality Modeling Mutation Nigeria North America Outcome Patient Care Patients Publishing Recruitment Activity Research Research Infrastructure Research Personnel Residual state Resources Sampling Severities Sickle Cell Sickle Cell Anemia Technology Testing Thalassemia Training Training and Education United States National Institutes of Health Universities Variant West Indies base clinical care cohort college experience genome wide association study improved insight interest medical schools novel parent grant programs

项目摘要

DESCRIPTION (provided by applicant): This research will be done primarily in Ibadan, Nigeria at the University of Ibadan and in Kingston, Jamaica at the University of the West Indies in collaboration with Richard Cooper, as an extension of NIH Grant No. R01HL053353, 6/15/09-4/30/14. Hemoglobinopathies are the most common monogenic disorders in the world. Recent findings indicate that genetic variation associated with fetal hemoglobin (HbF) levels strongly influences severity in patients with sickle cell disease (SCD) and 2-thalassemia, offering potential insights into novel therapies. Despite the high prevalence of SCD in West Africa, relatively little research has been conducted in this region utilizing modern genomic technology. In addition, life expectancy of patients with SCD has been greatly extended in industrialized countries, in part as a result of improved medical management. However management of SCD and development of comprehensive life-course care has lagged behind in Africa. A South-South collaboration between Jamaica and Nigeria provides an excellent opportunity to transfer advances in clinical care for SCD that are appropriate for low resources countries. In this project we propose to build on two decades of collaborative research in the West African diaspora to link investigators in Nigeria and Jamaica with institutions in North America to build research capacity in SCD and advance our understanding of the genetic influences on severity. We further propose to enhance the clinical SCD activities at the collaborating institution in Nigeria, provide training for our Nigerian collaborator, and create a model for outcomes and management research in the region. The specific aims of this project are 1) to establish a research collaboration between investigators at the University College Hospital (UCH), Ibadan, Nigeria, the University of the West Indies (UWI), Mona, Kingston, Jamaica, and Loyola Medical School, Chicago, USA to study genes which modify severity and clinical outcomes in SCD; 2) to share the clinical expertise from the 40-year experience of the Sickle Cell Unit, UWI, Mona to enhance the patient care of SCD at UCH, Ibadan; 3) to collect DNA and phenotypic information on 300 homozygous sickle cell patients from Ibadan; and 4) to perform association tests for and HbF levels and clinical severity with loci previously shown to modify HbF expression. We anticipate that this project will provide pilot data for a large-scale study of the clinical and genetic aspects of SCD in the Nigerian context. The samples and clinical data base can serve as the basis for future research, including extensive re-sequencing of key loci influencing HbF to identify causal mutations.

描述（由申请人提供）：这项研究将主要在尼日利亚的伊巴丹，伊巴丹大学和牙买加西印度群岛大学的金斯敦与理查德·库珀（Richard Cooper）合作，作为NIH授予号R01HL053353，6/15/09-4/30/30/14。血红蛋白病是世界上最常见的单基因疾病。最近的发现表明，与胎儿血红蛋白（HBF）水平相关的遗传变异对镰状细胞疾病（SCD）和2-甲性疾病患者的严重程度强烈影响，从而提供了对新疗法的潜在见解。尽管西非SCD的患病率很高，但利用现代基因组技术的该地区的研究很少。此外，SCD患者的预期寿命在工业化国家大大延长，部分原因是医疗管理的改善。但是，SCD的管理和全面的生活道路护理的发展落后于非洲。牙买加和尼日利亚之间的南南合作为SCD的临床护理发展提供了一个绝佳的机会，适合低资源国家。在这个项目中，我们建议在西非侨民的二十年合作研究基础上，将尼日利亚和牙买加的研究人员与北美机构联系起来，以在SCD中建立研究能力，并促进我们对严重性遗传影响的理解。我们进一步建议在尼日利亚的合作机构中加强SCD活动，为我们的尼日利亚合作者提供培训，并为该地区的成果和管理研究创建模型。该项目的具体目的是1）在大学学院医院（UCH），伊巴丹，尼日利亚，西印度群岛大学（UWI），MONA，KINGSON，JAMAICA和LOYOLA医学院的研究人员之间建立研究合作，以修改SCD中的丧失和临床成果； 2）分享来自UWI的40年经验的临床专业知识，以增强伊巴丹UCH的SCD患者护理； 3）收集来自伊巴丹的300名纯合镰状细胞患者的DNA和表型信息； 4）对先前显示的基因座进行了对HBF表达的改性，对HBF水平和临床严重程度进行关联测试。我们预计该项目将为尼日利亚环境中SCD的临床和遗传方面进行大规模研究提供试验数据。样本和临床数据库可以作为未来研究的基础，包括对关键基因座的广泛重新续订影响HBF以鉴定因果突变。