| Project/Area Number |
13204095
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | International Medical Center of Japan (Research Institute) |
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Principal Investigator |
KATO Norihiro International Medical Center of Japan (Research Institute), Dept. of Gene Diagnostics and Therapeutics, Director, 遺伝子診断治療開発研究部, 部長 (80293934)
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| Co-Investigator(Kenkyū-buntansha) |
YANAI Kazuyuki International Medical Center of Japan (Research Institute), Dept. of Gene Diagnostics and Therapeutics, Laboratory Chief, 遺伝子診断治療開発研究部, 室長 (30360704)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥36,400,000 (Direct Cost: ¥36,400,000)
Fiscal Year 2004: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2003: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2002: ¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2001: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | Salt sensitivity / Hypertension / Genetic analysis / Ethnic specificity / Water-electrolyte homeostasis / Natriuretic peptide |
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| Research Abstract |
In the present study, we have focused on salt sensitivity as a target 'intermediate' phenotype to investigate genetic susceptibility for hypertension. Despite a number of vigorous studies performed to date on this phenotype, any uniform definitions and measurement protocols have not been well established for the evaluation of salt sensitivity, and therefore, comparisons of the results among different studies cannot be made easily. Under these circumstances, we first devised a practical protocol to evaluate salt sensitivity in a population-based setting and then we applied it to select an appropriate set of SNPs that are useful for predicting salt sensitivity in the Japanese population.
Our principal study achievements are as follows: (1) In a total of 34 candidate genes selected for salt sensitivity, we sought tag SNPs by re-sequencing genomic DNA fragments derived from 48 individuals and we chose 166 tag SNPs among 471 SNPs thus detected; (2) In a population-based study panel comprising 95 unrelated individuals, we found two SNPs-one from AGTR2 and the other from ACE-to be significantly associated with salt sensitivity phenotypes when a pairwise association was tested by the chi-squared test statistics. Also, we found that 6 SNPs and two hormonal parameters-plasma renin activity and atrial natriuretic peptide concentration-can account for >50 % of variances (R-square) in blood pressure changes upon salt sensitivity intervention; (3) Based on the preliminary results obtained in the Japanese, we further performed a pilot study in the African blacks (n=60) and will start a main study in Tanzania; and (4) we identified two major quantitative trait loci (QTLs) for blood pressure influenced by salt loading i.e., salt sensitive hypertension, on rat chromosomes 1 and 3 and we are performing the positional cloning in each chromosomal region by using the congenic strategy.
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