Genetic Epidemiology Network of Salt Sensitivity (GenSalt) A NIH-sponsored family intervention study to identify novel genes for high blood pressure Investigators
Jiang He, MD, PhD, Principal Investigator
Jing Chen, Co-Investigator
Paul Muntner, PhD, Co-Investigator
Paul K. Whelton, MD, MSc, Co-Investigator Funding Agent
National Heart, Lung, and Blood Institute, NIH Participating Institutes
Chinese Academy of Medical Sciences
Chinese National Human Genome Center, Beijing
Tulane University
University of Texas Health Science Center at Houston
Washington University in St. Louis Description
Essential hypertension is a complex disease determined by both genetic and environmental factors and their interactions. The overall objective of the GenSalt 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 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 blood pressure or stage-1 hypertension (systolic blood pressure 130–160 mm Hg and diastolic blood pressure 85–100 mm Hg) from rural China. We will collect baseline information on medical history, lifestyle risk factors, anthropometrical measures, blood pressure, and blood measures (renin activity, angiotensin converting enzyme, 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 (one 24-hour and two overnight) in the siblings. We will conduct a cold pressor test at baseline (day 2 or 3) in all participants. We will conduct the following nutritional interventions in the siblings: a 1-week low sodium-feeding study (3 grams of salt or 51.3 mmol of sodium per day) on days 4–10, a 1-week high sodium-feeding study (18 grams of salt or 307.8 mmol of sodium per day) on days 11–17, and a 1-week oral potassium supplementation (60 mmol potassium/day on days 18–24). We will measure blood pressure on days 2, 5, 6, and 7 during each intervention period and collect one 24-hour and 2 overnight urinary specimens to measure sodium and potassium excretion on days 5, 6, and 7. We will perform genotyping for genome-wide linkage scans and for candidate genes in all siblings and their parents. Blood pressure 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 blood pressure 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 blood pressure. 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 patient. |
