Biochemical and Genetic Markers of Hypertension in Women

描述(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后果的主要风险因素。在黑人女性中，高血压更普遍，治疗控制不佳，比白人具有更具破坏性的健康结果，原因尚不清楚。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然研究得较少。数据将来自妇女健康倡议观察性研究(WHI-OS)，该研究由年龄在50岁至79岁的93,676名不同种族的绝经后妇女组成，拥有广泛的临床和问卷数据。在800对病例对照中(白人和黑人妇女各400对)，总计1600名受试者中，三个假说将在一项嵌套的高血压病例对照研究中得到验证。首先，我们将评估炎症标志物--C反应蛋白、白介素6、白介素1、8、肿瘤坏死因子-α受体2、sLCAM-1和基质金属蛋白酶-9--是否与白人和黑人女性高血压风险有关。其次，我们将研究与上述炎症生物标记物相关的六个新的多态--CRP、IL-6、IL-113、TNF-a、slCAM-1和MMP-9基因--以及另外两个与炎症和代谢综合征相关的多态--脂联素和PPAR-y2基因--寻找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，综合评估上述基因的重要单核苷酸多态，并检查白人和黑人女性常见单倍型与高血压风险的相关性。力量是极好的；对于每个生化标记物，我们有80%的力量来检测高血压的相对风险(RR)跨五分位数的趋势，比较第五和第一五分位数，分析800个病例对照对的1.49和分析400个病例对照对的1.74。对于每个遗传标记，我们有80%的能力来检测高血压的等位基因的加性效应，800个病例对照对的RR为1.36,400个病例对照对的RR为1.57。由于队列组装、随访、采血、储存和终点记录所需的巨额成本已经得到支持，WHI-OS为研究高血压提供了极其经济高效的研究环境。这项应用检查了来自广泛种族和社会背景的一大群妇女中发生高血压的有希望的生化和遗传标记，这些结果可能会影响普通人群中的高血压预防。

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.