Genetics of Hypertension

高血压的遗传学

• 批准号: 7526652
• 负责人: BINA JOE
• 金额: $ 45.37万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7526652
• 关键词: ADAMTS; Affect; Alleles; Animal Model; Antibodies; Blood Pressure; C-terminal; CD36 gene; Candidate Disease Gene; Cardiovascular system; Chromosomes, Human, Pair 1; Chronic; Clinic; Clinical; Cloning; Code; Collaborations; Condition; Congenic Strain; Dahl Hypertensive Rats; Data; Development; Disintegrins; Dissection; End Point; Endopeptidases; Enzyme Precursors; Enzymes; Essential Hypertension; Etiology; Event; Funding; Genes; Genetic; Genetic Determinism; Genetic Models; Genetic Recombination; Genetic Variation; Genomic Segment; Genomics; Human; Hypertension; Hypotension; Investigation; Knowledge; Laboratories; Link; Location; Maps; Medical; Metalloproteases; Mixed Function Oxygenases; Modeling; Nucleotides; Peptide Hydrolases; Personal Satisfaction; Play; Predisposition; Process; Proline; Public Health; Quantitative Trait Loci; Rate; Rattus; Reagent; Research; Resolution; Role; Serine; Single Nucleotide Polymorphism; Site; Structure-Activity Relationship; System; Testing; Threonine; Transgenic Organisms; Translating; Validation; Variant; Work; authority; base; blood pressure regulation; congenic; desire; familial hypertension; functional outcomes; gene discovery; gene function; human study; improved; normotensive; novel; polypeptide; rat genome; research study

DESCRIPTION (provided by applicant): Hypertension is the most common chronic medical condition worldwide and in the US alone 72 million people are affected with the condition. Of these, 90% developed 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 remain largely unknown. This 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 a 793.5 kb region on the rat genome as responsible for controlling BP. This region in rats and the orthologous regions in humans, contains two genes, only one of which contains significant variations. Analysis of single nucleotide polymorphisms in humans indicates that select variants of this gene are also associated with human essential hypertension. This observation defines the need to further investigate the function of this novel gene, which constitutes one of the specific aims of our proposal. The other aims are to further genetically dissect the critical 793.5kb region to obtain further evidence for the candidacy of this prioritized candidate gene and/or other QTL effectors by trapping the BP effect within the shortest possible rat genomic segment and to construct a transgenic-congenic strain to test the QTL effect. The significance of our proposal is that it is potentially on the verge of unraveling a novel genetic factor in the etiology of Essential Hypertension. PUBLIC HEALTH RELEVANCE: 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 pin-point at least one genetic factor that has not been previously suspected to cause hypertension.

描述（由申请人提供）：高血压是全球最常见的慢性病，​​仅在美国，有7200万人就会受到这种疾病的影响。其中，有90％的人出于未知原因出现高血压，也称为必不可少的高血压。尽管众所周知，遗传学在赋予发展基本高血压的敏感性方面起着重要作用，但因果关系负责基本高血压的基因/遗传因素的身份仍然很大程度上尚不清楚。这是促进我们对基本高血压病因的理解的最大限制因素。使用大鼠遗传模型进行高血压，我们在大鼠基因组上找到了一个793.5 kb的区域，以控制BP。大鼠和人类的直系同源区域中的该区域包含两个基因，其中一个基因包含显着变化。人类中单核苷酸多态性的分析表明，该基因的某些变体也与人类基本高血压有关。该观察结果定义了进一步研究该新基因的功能的必要性，该基因构成了我们建议的特定目的之一。另一个目的是进一步剖析关键的793.5kb区域，以获得进一步的证据证明该优先级候选基因和/或其他QTL效应子通过将BP效应捕获在最短的大鼠基因组段中并构建转基因菌株以测试QTL效应，从而获得了BP效应，从而获得了进一步的证据。我们提议的意义在于，它可能处于基本高血压病因中的新遗传因素的边缘。公共卫生相关性：遗传学被广泛认为是有助于高血压发展的重要因素，这导致了心血管相关的疾病。该提案中描述的研究工作涉及改善我们当前对控制血压的基因身份的理解。通过成功完成所描述的工作获得的知识将至少将一个遗传因素固定为以前尚未怀疑引起高血压的遗传因素。