Genetic Elements Controlling Blood Pressure

说明(申请人提供)：在所有合并的高血压患者中，90%的患者出现不明原因的高血压，也称为原发性高血压。虽然众所周知，遗传学在原发性高血压的易感性中起着重要作用，但导致原发性高血压的基因/遗传因素的特性在很大程度上仍不清楚，这是推动我们对原发性高血压病因学的了解的最大限制因素。利用高血压的大鼠遗传模型，我们在大鼠基因组上定位了负责控制BP的区域。如果这个区域被定位到单个基因元素的分辨率，那么就可以用来查询类似的基因元素，作为人类高血压的原因。因此，我们建议的目的是在我们已经精细绘制的三个区域上确定BP的遗传决定因素。我们的建议的意义在于，它潜在地处于解开原发性高血压病因学中新的遗传因素的边缘。公共卫生评论：众所周知，遗传学是导致高血压发展的一个重要因素，高血压会导致心血管相关疾病。这项提案中描述的研究工作是为了改善我们目前对控制血压的基因的身份的认识，这一认识非常有限。通过成功完成所述工作而获得的知识有望确定以前未被怀疑会导致高血压的遗传因素。

DESCRIPTION (provided by applicant): Among all the hypertensive subjects combined, >90% develop hypertension for no known reasons, also called as Essential hypertension. Although it is well known that genetics play a major role in conferring susceptibility to develop essential hypertension, the identities of the genes/genetic factors that are causally responsible for essential hypertension remaining largely unknown is the single biggest rate-limiting factor in advancing our understanding of the etiology of essential hypertension. Using a rat genetic model for hypertension, we have located regions on the rat genome as responsible for controlling BP. This region, if mapped to the resolution of single genetic elements, can then be utilized for querying similar genetic elements as causative of hypertension in humans. The aims of our proposal are to therefore identify the genetic determinants of BP on three regions that we have already fine-mapped. The significance of our proposal is that it is potentially on the verge of unraveling novel genetic factors in the etiology of Essential Hypertension. PUBLIC HEALTH REVELANCE: Genetics is well recognized to be an important factor that contributes to the development of hypertension, which leads to cardiovascular related illnesses. The research work described in this proposal pertains to improve our current, significantly limited understanding of the identities of genes that control blood pressure. Knowledge gained through successful completion of the work described is expected to identify genetic factors that have not been previously suspected to cause hypertension.