Essential hypertension is a complex disease determined by both genetic and environmental factors and their interactions. The overall objective of the proposed study is to identify susceptibility genes for hypertension in human populations.
The specific aims are to localize and identify novel genes related to variation in blood pressure (BP) responses to a low dietary sodium intake, a high dietary sodium intake, oral potassium supplementation, and cold pressor test. The proposed study will utilize a family intervention study design. We will recruit 750 sibships (n=1750 siblings) and their parents (n=1250) from 500 families, each family ascertained through a proband who has untreated high normal BP or stage-1 hypertension (systolic BP 130-160 mm Hg and diastolic BP 85-100 mm Hg) from rural China. We will collect baseline information on medical history, lifestyle risk factors, anthropometric measures, BP, and blood measures (renin activity, ACE, angiotensin II, natriuretic peptide, glucose, insulin, and lipids) in all participants, and dietary nutrient intake (three 24-hour recalls) and urinary sodium and potassium excretion (three 24-hour) in the siblings. We will conduct the following interventions in the siblings: a cold pressor test at baseline (day 2 or 3), a 1-week low sodium-feeding study (40 mmol sodium/day on days 4-10), a 1-week high sodium-feeding study (280 mmol sodium/day on days 11-17), and a 1-week oral potassium supplementation (90 mmol potassium/day on days 18-24). We will measure BP and 24-hour urinary sodium and potassium excretion during the last 3 days of each intervention period. We will perform genotyping for genome-wide linkage scans and for candidate genes in all siblings and their parents. BP responses to the interventions will be analyzed primarily as quantitative traits. The primary analyses include linkage analysis, transmission/disequilibrium test, and association analysis between genetic markers and BP responses to the interventions. Our study will identify novel genes that interact significantly with the effect of dietary sodium and potassium intake or cold pressor on BP. This information is useful for early identification of individuals at high risk for hypertension and for development of targeted lifestyle modification for the primary prevention of hypertension. This information is also useful for designing tailored lifestyle interventions for the treatment of hypertension among individual patients.
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