GENETIC DETERMINANTS OF HIGH BLOOD PRESSURE

高血压的遗传决定因素

• 批准号: 6056309
• 负责人: JEAN-MARC LALOUEL
• 金额: $ 55.82万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-05 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6056309
• 关键词: angiotensinogen; cooperative study; disease /disorder classification; disease /disorder proneness /risk; epidemiology; essential hypertension; family genetics; genetic mapping; genetic markers; genetic polymorphism; genome; genotype; human genetic material tag; human subject; linkage mapping; molecular genetics; polymerase chain reaction; single strand conformation polymorphism

The HyperGEN Molecular Genetics Laboratory will perform the marker studies required for linkage analysis and tests of association, proceeding through the following steps: (1) markers will be generated for a series of up to 20 candidate genes of particular significance in blood pressure regulation; (2) preliminary experiments will establish the specifics of a large-scale genotyping strategy by a unique, automated deep-multiplexing technology; (3) reference marker frequencies needed for linkage analysis will be determined in random controls; the candidate genes will be examined for genetic linkage in three series of hypertensive siblings: (4) a pre-existing Utah sample set including 245 sibling pairs, and (5) two series of HyperGEN 'severe' hypertensive siblings (1,400 subjects generating 1,000 sibling pairs); (6) thereafter, a genome-wide linkage search involving 240 markers will be performed in these two HyperGEN series; (7) assuming that linkage is found and confirmed for up to 5 loci, their possible contribution to milder forms of hypertension will be tested in two HyperGEN samples; (8) of these 5 loci, it is assumed that 3 known genes will become the focus of a systematic search for molecular variants in a collection of 100 random controls of each ethnic group, followed by case-control comparisons between hypertensive probands and normotensive controls; (9) for any marker exhibiting significant association, genotyping will be extended to all relatives and random controls for the purpose of multivariate genetic and epidemiological studies.

HyperGEN分子遗传学实验室将进行标记研究 进行关联分析和关联测试， 以下步骤：（1）标记将产生一系列高达 20个在血压中具有特殊意义的候选基因 （2）初步实验将建立一个具体的 通过独特的自动化深度多路复用的大规模基因分型策略 技术;（3）连锁分析所需的参考标记频率 将在随机对照中确定;候选基因将 在三组高血压同胞中检查遗传连锁：（4） 预先存在的犹他州样本集，包括245个同胞对，和（5）两个 HyperGEN“重度”高血压同胞系列（1，400例受试者 产生1，000对兄弟姐妹）;（6）此后，全基因组连锁 将在这两个HyperGEN中进行涉及240个标记物的检索 系列;（7）假设发现并确认了多达5个基因座的连锁， 他们对轻度高血压的可能贡献将被测试 在两个HyperGEN样品中;（8）在这5个基因座中，假设3个已知的基因座是 基因将成为分子变异系统搜索的焦点 在每个种族组的100个随机对照组中， 高血压先证者与血压正常者的病例对照比较 对照;（9）对于任何表现出显著关联的标记物， 基因分型将扩展到所有亲属和随机对照， 多变量遗传学和流行病学研究的目的。

项目成果

Novel genetic variants contributing to left ventricular hypertrophy: the HyperGEN study.

• DOI: 10.1097/hjh.0b013e32832be612
• 发表时间: 2009-08
• 期刊: Journal of hypertension
• 影响因子: 4.9
• 作者: Arnett DK;Devereux RB;Rao DC;Li N;Tang W;Kraemer R;Claas SA;Leon JM;Broeckel U
• 通讯作者: Broeckel U

Blood pressure responses to acute stress and left ventricular mass (The Hypertension Genetic Epidemiology Network Study).

血压对急性应激和左心室质量的反应（高血压遗传流行病学网络研究）。

• DOI: 10.1016/s0002-9149(01)02305-0
• 发表时间: 2002
• 期刊: The American journal of cardiology
• 作者: al'Absi,Mustafa;Devereux,RichardB;Lewis,CoraE;Kitzman,DalaneW;Rao,DabeeruC;Hopkins,Paul;Markovitz,Jerome;Arnett,DonnaK
• 通讯作者: Arnett,DonnaK

Plasma adiponectin concentrations and correlates in African Americans in the Hypertension Genetic Epidemiology Network (HyperGEN) study.

高血压遗传流行病学网络 (HyperGEN) 研究中非裔美国人的血浆脂联素浓度及其相关性。

• DOI: 10.1016/j.metabol.2007.03.020
• 发表时间: 2007
• 期刊: Metabolism: clinical and experimental
• 作者: Shikany,JamesM;Lewis,CoraE;Freedman,BarryI;Arnett,DonnaK;Leiendecker-Foster,Catherine;Jones,TamekiaL;Redden,DavidT;Oberman,Albert
• 通讯作者: Oberman,Albert

Evidence for a gene influencing fasting LDL cholesterol and triglyceride levels on chromosome 21q.

21q 染色体上存在影响空腹 LDL 胆固醇和甘油三酯水平的基因的证据。

• DOI: 10.1016/j.atherosclerosis.2004.09.009
• 发表时间: 2005
• 期刊: Atherosclerosis.
• 作者: North,KariE;Miller,MichaelB;Coon,Hilary;Martin,LisaJ;Peacock,JamesM;Arnett,Donna;Zhang,Binbin;Province,Michael;Oberman,Albert;Blangero,John;Almasy,Laura;Ellison,RCurtis;Heiss,Gerardo
• 通讯作者: Heiss,Gerardo

A combined analysis of genomewide linkage scans for body mass index from the National Heart, Lung, and Blood Institute Family Blood Pressure Program.

• DOI: 10.1086/340362
• 发表时间: 2002-05
• 期刊: American journal of human genetics
• 影响因子: 9.8
• 作者: Xiaodong Wu;R. Cooper;I. Borecki;C. Hanis;M. Bray;C. Lewis;Xiaofeng Zhu-;Donghui Kan;A. Luke;David Curb