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疾病，仅在美国就有7200万人患有这种疾病。其中，90%的人因不明原因而患上高血压，也称为原发性高血压。虽然众所周知，遗传学在赋予原发性高血压的易感性方面起着重要作用，但导致原发性高血压的基因/遗传因素的身份仍然很大程度上未知。这是提高我们对原发性高血压病因学认识的最大限速因素。使用大鼠高血压遗传模型，我们已经在大鼠基因组上定位了一个793.5 kb的区域，负责控制BP。大鼠的这一区域和人类的正向区域包含两个基因，其中只有一个包含显著的变异。对人类单核苷酸多态性的分析表明，该基因的选择变体也与人类原发性高血压相关。这一观察结果确定了进一步研究这种新基因功能的必要性，这构成了我们提案的具体目标之一。另一个目的是进一步的遗传解剖的关键793.5kb的区域，以获得进一步的证据，这个优先的候选基因和/或其他QTL效应的候选资格，通过捕获的BP效应在最短的可能的大鼠基因组片段，并构建一个转基因-同源株来测试QTL效应。我们的建议的意义在于，它可能即将揭开原发性高血压病因学中的一种新的遗传因素。公共卫生相关性：遗传被公认为是导致高血压发展的重要因素，高血压导致心血管相关疾病。本提案中描述的研究工作有助于改善我们目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有望确定至少一种先前未被怀疑导致高血压的遗传因素。