GENE POLYMORPHISM & BLOOD PRESSURE REGULATION

高血压是一种由遗传和环境因素相互作用引起的多因素疾病，但其致病基因尚未明确。以前对候选基因的研究对于主基因在高血压发病中的作用给出了不同的结果。原因尚不清楚，但可能是由于种群差异、分析方法的局限性、对人类疾病动物模型的错误假设、未能考虑基因与环境的相互作用等。这是一项由霍华德大学和波士顿大学医学院参与的合作研究。波士顿大学医学中心诊所的种族混血预计将有50%是黑人后裔，50%是高加索人。为了成功地开展这一项目，我们将从霍华德大学医学中心附属的几个高血压门诊确定的50个有多个在世成员和500个受影响同胞对的家系中收集血样、家族史和临床信息。我们将收集这些人的血液样本进行DNA分析，将在波士顿的SCOR核心实验室进行，直到霍华德大学DNA分析实验室建立为止。来自正常血压控制受试者的数据将来自弗雷明翰心脏研究和高血压家族的配偶。这项建议的具体目标是：1)从染色体座位对受试者进行基因分型，2)分析与高血压连锁的遗传标记数据，3)确认AIM#2中确定的正连锁，并使用连锁不平衡和DNA池方法在高血压病例组和正常血压对照组中确定特定的等位基因关联，以及4)筛选和评估与高血压相关的候选基因突变。

Essential hypertension is a multifactorial disorder resulting from the interaction of heredity and environmental factor, but the genes responsible have not yet been defined. Previous studiesof candidate loci have given mixed results about the role of major genes in the development of hypertension. The reasons for this are unclear, but could be due to population differences, limitations of analytic methods, incorrect assumptions about animal models of the human disease, failure to account for gene-environment interactions, etc. This is a collaborative study involving the Howard University and Boston University Schools of Medicine. The racial mix at the Boston University Medical Center's clinics is expected to be 50% of Black descent and 50% Caucasians. In order to successfully carry out this project, we will collect blood samples, family histories, and clinical information from 50 kindreds with multiple living affected members and 500 affected sib-pairs, ascertained from several outpatient hypertension clinics affiliated with the Howard University Medical Center. We will collect blood specimens from these individuals for DNA analysis, to be performed at the SCOR Core Laboratory in Boston, until the Howard University DNA Analysis Laboratory is established. Data from normotensive control subjects will be available from the Framingham Heart Study and from the spouces in the hypertensive kindreds. The Specific Aims of this proposal are: 1) To genotype the subjects from chromosomal loci, 2) To analyze the genetic marker data for linkage to hypertension, 3) To confirm positive linkages identified in aim #2 and to identify particular allele association in groups of hypertensive cases and normotensive controls using methods of linkage disequilibrium and DNA pooling, and 4) To screen for and assess mutations in candidate genes linked to hypertension in patients and controls.