Biochemical and Genetic Markers of Hypertension in Women

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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.