Biochemical and Genetic Markers of Hypertension in Women

女性高血压的生化和遗传标志物

• 批准号: 6928986
• 负责人: HOWARD D SESSO
• 金额: $ 38.87万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6928986
• 关键词: African American; acute phase protein; biomarker; cardiovascular disorder epidemiology; cardiovascular disorder risk; caucasian American; cell adhesion molecules; clinical research; female; genetic markers; human data; hypertension; inflammation; interleukin 1; interleukin 6; metabolic syndrome; metalloendopeptidases; peroxisome proliferator activated receptor; postmenopause; racial /ethnic difference; single nucleotide polymorphism; women' s health

DESCRIPTION (provided by applicant): Hypertension affects up to 50 million Americans, and is a major risk factor for cardiovascular disease and other health outcomes. Among Black women, hypertension is more prevalent, less well controlled by treatment, and has more damaging health outcomes versus Whites for reasons still unclear. While several lifestyle and dietary factors are associated with hypertension, relevant biochemical and genetic markers remain less well studied. Data will be used from the Women's Health Initiative Observational Study (WHI-OS), a cohort of 93,676 ethnically diverse postmenopausal women aged 50 to 79 years with extensive clinical and questionnaire data. Three hypotheses will be tested in a nested case-control study of incident hypertension in 800 case-control pairs (400 each of White and Black women), totaling 1,600 subjects. First, we will assess whether markers of inflammation - CRP, IL-6, IL-1,8, TNF-a receptor 2, slCAM-1, and MMP-9 - are associated with the risk of hypertension in White and Black women. Second, we will examine six novel polymorphisms linked to the above inflammatory biomarkers - the CRP, IL-6, IL-113, TNF-a, slCAM-1, and MMP-9 genes- and two other polymorphisms related to inflammation and the metabolic syndrome- the adiponectin and PPAR-y2 genes - for their potentially important associations with the risk of hypertension. Third, we will comprehensively evaluate important single-nucleotide polymorphisms in the above genes and examine associations between common haplotypes and hypertension risk in White and Black women, using state-of-the art genotyping technology and statistical methods. Power is excellent; for each biochemical marker, we have 80% power to detect a trend across quintiles for a relative risk (RR) of hypertension, comparing the fifth versus first quintiles, of 1.49 for analyses of 800 case-control pairs and 1.74 for analyses of 400 case-control pairs. For each genetic marker, we have 80% power to detect an additive effect of an allele for a RR of hypertension of 1.36 for 800 case-control pairs and 1.57 for 400 case-control pairs. Because the large costs needed for cohort assembly, follow-up, blood collection, storage, and endpoint documentation are already supported, the WHI-OS provides an extremely cost-effective research setting to study hypertension. This application examines promising biochemical and genetic markers of incident hypertension in a large group of women from a broad range of ethnic and social backgrounds, and these results have the potential to impact hypertension prevention in the general population.

描述（由申请人提供）：高血压影响多达 5000 万美国人，是心血管疾病和其他健康结果的主要危险因素。与白人相比，黑人女性的高血压更为普遍，治疗控制效果较差，并且对健康的损害更大，原因尚不清楚。虽然多种生活方式和饮食因素与高血压有关，但相关的生化和遗传标记的研究仍较少。将使用女性健康倡议观察性研究 (WHI-OS) 的数据，该研究由 93,676 名年龄在 50 至 79 岁的不同种族绝经后女性组成，具有广泛的临床和问卷数据。一项针对高血压的巢式病例对照研究将测试三个假设，该研究涉及 800 组病例对照对（白人和黑人女性各 400 名），总共 1,600 名受试者。首先，我们将评估炎症标志物 - CRP、IL-6、IL-1,8、TNF-a 受体 2、slCAM-1 和 MMP-9 - 是否与白人和黑人女性的高血压风险相关。其次，我们将检查与上述炎症生物标志物（CRP、IL-6、IL-113、TNF-a、slCAM-1 和 MMP-9 基因）相关的六种新多态性，以及与炎症和代谢综合征相关的另外两种多态性（脂联素和 PPAR-y2 基因），以了解它们与高血压风险的潜在重要关联。第三，我们将利用最先进的基因分型技术和统计方法，全面评估上述基因中重要的单核苷酸多态性，并研究常见单倍型与白人和黑人女性高血压风险之间的关联。动力极佳；对于每个生化标志物，我们有 80% 的功效来检测五分位数的高血压相对风险 (RR) 趋势，比较第五与第一五分位数，800 个病例对照对的分析为 1.49，400 个病例对照对的分析为 1.74。对于每个遗传标记，我们有 80% 的功效检测到等位基因的累加效应，其中 800 个病例对照对的高血压 RR 为 1.36，400 个病例对照对的高血压 RR 为 1.57。由于队列组装、随访、血液采集、储存和终点记录所需的巨额成本已经得到支持，因此 WHI-OS 为研究高血压提供了极具成本效益的研究环境。该应用在来自广泛种族和社会背景的大量女性中检查了高血压事件的有希望的生化和遗传标记，这些结果有可能影响普通人群的高血压预防。