GENE POLYMORPHISM & BLOOD PRESSURE REGULATION

原发性高血压是一种遗传和环境因素相互作用的多因素疾病，但相关基因尚未明确。先前对候选基因座的研究对主要基因在高血压发生中的作用给出了不同的结果。造成这种情况的原因尚不清楚，但可能是由于人口差异、分析方法的局限性、对人类疾病动物模型的错误假设、未能解释基因-环境相互作用等。这是一项涉及霍华德大学和波士顿大学医学院的合作研究。波士顿大学医学中心诊所的种族构成预计将是50%的黑人后裔和50%的高加索人。为了顺利开展该项目，我们将从霍华德大学医学中心附属的几个门诊高血压诊所收集50种有多名在世患者和500对患病兄弟姐妹的血液样本、家族史和临床信息。在霍华德大学DNA分析实验室建立之前，我们将收集这些人的血样进行DNA分析，并在波士顿的SCOR核心实验室进行。从弗雷明汉心脏研究和高血压类型的研究中可以获得血压正常的对照组的数据。本提案的具体目的是：1)从染色体位点对受试者进行基因分型，2)分析与高血压相关的遗传标记数据，3)通过连锁不平衡和DNA池化的方法确认目标#2中发现的正相关性，并在高血压病例组和正常对照组中确定特定的等位基因关联，4)筛选和评估患者和对照组中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.