Biochemical and Genetic Markers of Hypertension in Women

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。在黑人妇女中，高血压更普遍，治疗控制得不好，并且由于尚不清楚的原因，与白人相比具有更大的破坏性健康结果。虽然一些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仍缺乏充分的研究。将使用来自妇女健康倡议观察性研究（WHI-OS）的数据，该研究包括93，676名年龄在50至79岁之间的不同种族绝经后妇女，具有广泛的临床和问卷调查数据。将在800例病例对照对（白色和黑人女性各400例）（共计1，600例受试者）中对高血压事件的巢式病例对照研究中检验三个假设。首先，我们将评估炎症标志物- CRP、IL-6、IL-1、8、TNF-α受体2、sICAM-1和MMP-9 -是否与白色和黑人妇女的高血压风险相关。其次，我们将检查与上述炎症生物标志物相关的六种新的多态性-CRP、IL-6、IL-113、TNF-α、sICAM-1和MMP-9基因-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，我们将综合评估上述基因中的重要单核苷酸多态性，并使用最先进的基因分型技术和统计方法，研究常见单倍型与白色和黑人女性高血压风险之间的关联。权力是优秀的;对于每一个生化标志物，我们有80%的能力检测出五分位数之间高血压相对危险度（RR）的趋势，比较第五个五分位数和第一个五分位数，800个病例对照对的分析结果为1.49，400个病例对照对的分析结果为1.74。对于每一个遗传标记，我们有80%的权力来检测一个等位基因的高血压的RR为1.36的800例对照对和1.57的400例对照对的加性效应。由于队列集合、随访、血液采集、储存和终点记录所需的大量成本已经得到支持，WHI-OS为研究高血压提供了一个极具成本效益的研究环境。该应用程序检查了来自广泛种族和社会背景的一大群妇女中有希望的高血压事件的生化和遗传标记，这些结果有可能影响一般人群的高血压预防。

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.