? ? 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. ? ? ?
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