? ? The overall objective of this response to the limited competition RFA (HL-06-123) is to localize and identify quantitative trait loci (QTLs) and genetic variants that determine individuals' blood pressure (BP) responses to dietary salt and potassium intervention by using the extensive phenotype and genotype data as well as biological specimens already collected in the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt).
The specific aims are to examine the effect of environmental risk factors and physiological/ biochemical measures on BP responses to dietary sodium and potassium intervention; to conduct genome-wide linkage analyses on BP responses to dietary sodium and potassium intervention as well as cold pressor test using 407 microsatellite markers genotyped in GenSalt; to conduct genetic association analyses of BP responses to dietary sodium and potassium intervention as well as cold pressor test using 278 single nucleotide polymorphisms (SNPs) previously genotyped in 30 biological candidate genes; and to fine-map positional candidate genes under one most promising linkage peak with dense SNP mapping. GenSalt is a unique NHLBI-sponsored family feeding-study conducted in 3,153 participants from 658 families living in rural areas of northern China. Each GenSalt family was ascertained through a proband with untreated pre-hypertension or stage-1 hypertension identified from population BP screening. The dietary intervention, which included a 7-day low sodium-feeding (51.3 mmol/day), a 7-day high sodium-feeding (307.8 mmol/day), and a 7-day high sodium-feeding with an oral potassium supplementation (60 mmol/day), was conducted among 1,906 probands, sibs, spouses, and offspring within a continuous 3-week period. Three BP measurements were obtained on each of 3 days during the baseline and on the last 3 days of each of the 3 intervention periods. The proposed study has important public health and clinical implications. Establishing a relationship between genetic variants with salt-sensitivity and potassium-sensitivity will help identify individuals at high risk for hypertension and who should receive a low sodium and high potassium dietary intervention. In addition, identifying genes related to salt-sensitivity and potassium-sensitivity of BP should enable the discovery of new pharmaceutical treatment for hypertension. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL072507-06
Application #
7467985
Study Section
Special Emphasis Panel (ZHL1-CSR-K (F1))
Program Officer
Jaquish, Cashell E
Project Start
2002-09-30
Project End
2009-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
6
Fiscal Year
2008
Total Cost
$342,566
Indirect Cost
Name
Tulane University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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Gu, Xiaoying; Gu, Dongfeng; He, Jiang et al. (2018) Resequencing Epithelial Sodium Channel Genes Identifies Rare Variants Associated With Blood Pressure Salt-Sensitivity: The GenSalt Study. Am J Hypertens 31:205-211
Li, Changwei; Kim, Yun Kyoung; Dorajoo, Rajkumar et al. (2017) Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians. Circ Cardiovasc Genet 10:e001527
Zhang, Dingding; Gu, Dongfeng; He, Jiang et al. (2017) Associations of the Serum/Glucocorticoid Regulated Kinase Genes With BP Changes and Hypertension Incidence: The Gensalt Study. Am J Hypertens 30:95-101
Han, Xikun; Hu, Zunsong; Chen, Jing et al. (2017) Associations Between Genetic Variants of NADPH Oxidase-Related Genes and Blood Pressure Responses to Dietary Sodium Intervention: The GenSalt Study. Am J Hypertens 30:427-434
Nierenberg, Jovia L; Li, Changwei; He, Jiang et al. (2017) Blood Pressure Genetic Risk Score Predicts Blood Pressure Responses to Dietary Sodium and Potassium: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity). Hypertension 70:1106-1112
Li, Changwei; He, Jiang; Chen, Jing et al. (2017) Genome-Wide Gene-Potassium Interaction Analyses on Blood Pressure: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity). Circ Cardiovasc Genet 10:
Spracklen, Cassandra N; Chen, Peng; Kim, Young Jin et al. (2017) Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels. Hum Mol Genet 26:1770-1784
Chen, Yu; Wu, Fen; Saito, Eiko et al. (2017) Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium. Diabetologia 60:1022-1032
Li, Kuibao; Yao, Chonghua; Yang, Xinchun et al. (2017) Effect of Resting Heart Rate on All-Cause Mortality and Cardiovascular Events According to Age. J Am Geriatr Soc 65:989-994

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