HYPERTENSION IN A HIGH RISK ISOLATED USSR POPULATION

苏联高危人群中的高血压

• 批准号: 2291645
• 负责人: ROGER R WILLIAMS
• 金额: $ 2.35万
• 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: 1995-09-30 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2291645
• 关键词: Commonwealth of Independent States; DNA; United States; angiotensin /renin /aldosterone hypertension; angiotensinogen; blood chemistry; blood pressure; cardiovascular disorder epidemiology; dietary potassium; dietary sodium; disease /disorder proneness /risk; familial hypertension; family genetics; gene frequency; genetic markers; human genetic material tag; human subject; hyperinsulinism; hypertension; kallikreins; linkage mapping; longitudinal human study; nutrition related tag; phenotype; urinalysis

The genetic-epidemiology of intermediate phenotypes associated with familial hypertension is currently being studied in Utah pedigrees and sibships. Of primary interest are markers for the angiotensinogen locus, which has been linked to hypertension, urinary kallikrein excretion and dyslipidemia. The parent grants of this application are funded to perform sibpair and pedigree linkage of hypertension to intermediate phenotypes, including kallikrein, Na-Li countertransport, nonmodulation of the renin- angiotensin system and salt sensitivity. Serum cholesterol, triglycerides, insulin, and HDL-C are also being measured to investigate the syndrome of familial dyslipidemic hypertension. This syndrome associates dyslipidemia, hyperinsulinemia and obesity to early onset familial hypertension. The abnormal kallikrein and dyslipidemia phenotypes are common in the Utah population, and similar frequencies of dyslipidemia have been described in U.S. and European populations. The angiotensinogen marker is very common and has been linked to hypertension in three different populations (France, Utah, and Japan), suggesting that it will be found in the USSR also. There is also less cultural and dietary heterogeneity in the village of Nochur than in the U.S., providing an ideal population for genetic studies. This foreign collaboration will study kallikrein/renin/aldosterone/angiotensinogen and dyslipidemia/hyperinsulinemia in a unique population in the former U.S.S.R. The settlement of Nochur (approximately 6,000 persons, average age of 31) near the Iranian border has a high prevalence of early onset, severe hypertension, CHD and stroke. There are about 800 nuclear families arising from only a small number of clans. Blood pressures from 2342 persons in this population have already been obtained. The blood pressure distribution is significantly bimodal and 4% (N=l04) of measured persons have a diastolic blood pressure above 110 mmHg and 8% have systolic blood pressure greater than 180 mmHg. 37% are hypertensive by WHO criteria, making Nochur ideal to study candidate genes responsible for the high rates of hypertension. The specific aims of this application include a case-control study to relate intermediate phenotypes to blood pressure and to test for genetic association of candidate loci to hypertension and measured phenotypes. This will be followed by a family genetic study to look for major genes and environmental interactions. Nuclear families of 100 probands with the highest blood pressures will be selected as the high risk families. These 100 probands will be compared to 100 age- and gender-matched controls. Ml family members from the 100 high risk families will be screened. Medical family histories will be obtained from each nuclear family to join families together into individual clans which will be verified by DNA analysis. Genetic segregation and linkage analyses will test for the presence of major genes for measured phenotypes and hypertension, and results will be compared to the Utah population. DNA, plasma and urine will be frozen. DNA will be sent to Utah for genetic linkage and association analyses with candidate genes already available from the parent grant.

与 目前正在犹他州的家族性高血压正在研究， sibships。主要感兴趣的是血管紧张素原点的标记， 与高血压，尿kallikrein排泄和 血脂血症。该申请的父母赠款是为执行的 高血压与中间表型的SIBPAIR和血统 包括kallikrein，Na-Li反式转移，肾素的不调制 血管紧张素系统和盐敏感性。血清胆固醇，甘油三酸酯， 还测量了胰岛素和HDL-C以研究综合征 家族性血脂性高血压。该综合征会使血脂异常， 高胰岛素血症和肥胖症早期发作家族性高血压。这 异常的kallikrein和血脂异常表型在犹他州很常见 在 美国和欧洲人口。血管紧张素原标志物非常常见 并与三个不同人群中的高血压联系在一起 （法国，犹他州和日本），建议将其在苏联找到 还。村里的文化和饮食异质性也较少 诺丘（Nochur）比在美国为遗传提供了理想的人群 研究。 这种外国合作将学习 kallikrein/肾素/醛固酮/血管紧张素原和 前者独特人群的血脂异常/高胰岛素血症 us.s.r. Nochur的和解（大约6,000人，平均 31岁）在伊朗边境附近的早期发病率很高， 严重的高血压，冠心病和中风。大约有800个核家庭 仅由少数氏族产生。 2342的血压 该人群中的人已经获得。血压 分布显着为双峰，被测量人员的4％（n = l04） 舒张压高于110 mmHg，有8％的血压有收缩血 压力大于180 mmHg。 37％的人是谁的标准，是高血压 使Nochur理想研究候选基因负责高的基因 高血压率。 本应用的具体目的包括一项案例对照研究 将中间表型与血压相关联并测试遗传 候选基因座与高血压和测量表型的关联。 随后将进行家庭遗传研究，以寻找主要基因 和环境互动。 100个核心家庭 最高的血压将被选为高风险家庭。这些 将100个概率与100个年龄和性别匹配的对照进行比较。 ML 将筛选来自100个高风险家庭的家庭成员。医疗的 家庭历史将从每个核心家庭获得加入 家庭一起进入单个氏族，将通过DNA验证 分析。遗传分离和连锁分析将测试 存在用于测量表型和高血压的主要基因，以及 结果将与犹他州人口进行比较。 DNA，血浆和尿液 将被冻结。 DNA将被派往犹他州进行遗传联系和 与已经可从可用的候选基因分析的关联分析 父母赠款。