Among all the hypertensive subjects combined, >90% develop hypertension for no known reasons, also called as Essential hypertension. Although it is well known that genetics play a major role in conferring susceptibility to develop essential hypertension, the identities of the genes/genetic factors that are causally responsible for essential hypertension remaining largely unknown is the single biggest rate-limiting factor in advancing our understanding of the etiology of essential hypertension. Using a rat genetic model for hypertension, we have located regions on the rat genome as responsible for controlling BP. This region, if mapped to the resolution of single genetic elements, can then be utilized for querying similar genetic elements as causative of hypertension in humans.
The aims of our proposal are to therefore identify the genetic determinants of BP on three regions that we have already fine-mapped. The significance of our proposal is that it is potentially on the verge of unraveling novel genetic factors in the etiology of Essential Hypertension. PUBLIC HEALTH REVELANCE: Genetics is well recognized to be an important factor that contributes to the development of hypertension, which leads to cardiovascular related illnesses. The research work described in this proposal pertains to improve our current, significantly limited understanding of the identities of genes that control blood pressure. Knowledge gained through successful completion of the work described is expected to identify genetic factors that have not been previously suspected to cause hypertension.

Public Health Relevance

Genetics is well recognized to be an important factor that contributes to the development of hypertension, which leads to cardiovascular related illnesses. The research work described in this proposal pertains to improve our current, significantly limited understanding of the identities of genes that control blood pressure. Knowledge gained through successful completion of the work described is expected to identify genetic factors that have not been previously suspected to cause hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL020176-33
Application #
7798169
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Thrasher, Terry N
Project Start
1988-06-01
Project End
2013-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
33
Fiscal Year
2010
Total Cost
$564,433
Indirect Cost
Name
University of Toledo
Department
Physiology
Type
Schools of Medicine
DUNS #
807418939
City
Toledo
State
OH
Country
United States
Zip Code
43614
Haller, Steven T; Kumarasamy, Sivarajan; Folt, David A et al. (2017) Targeted disruption of Cd40 in a genetically hypertensive rat model attenuates renal fibrosis and proteinuria, independent of blood pressure. Kidney Int 91:365-374
Kumarasamy, Sivarajan; Solanki, Sumeet; Atolagbe, Oluwatomisin T et al. (2017) Deep Transcriptomic Profiling of M1 Macrophages Lacking Trpc3. Sci Rep 7:39867
Yeoh, Beng San; Aguilera Olvera, Rodrigo; Singh, Vishal et al. (2016) Epigallocatechin-3-Gallate Inhibition of Myeloperoxidase and Its Counter-Regulation by Dietary Iron and Lipocalin 2 in Murine Model of Gut Inflammation. Am J Pathol 186:912-26
Yeoh, Beng San; Saha, Piu; Singh, Vishal et al. (2016) Deficiency of stearoyl-CoA desaturase-1 aggravates colitogenic potential of adoptively transferred effector T cells. Am J Physiol Gastrointest Liver Physiol 311:G713-G723
Nie, Ying; Kumarasamy, Sivarajan; Waghulde, Harshal et al. (2016) High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass. Physiol Genomics 48:409-19
Oh, Young S; Appel, Lawrence J; Galis, Zorina S et al. (2016) National Heart, Lung, and Blood Institute Working Group Report on Salt in Human Health and Sickness: Building on the Current Scientific Evidence. Hypertension 68:281-8
Cheng, Xi; Waghulde, Harshal; Mell, Blair et al. (2016) Pleiotropic Effect of a High Resolution Mapped Blood Pressure QTL on Tumorigenesis. PLoS One 11:e0153519
Bai, Yan; Wu, Jian; Li, Daxiang et al. (2016) Differential roles of caveolin-1 in ouabain-induced Na+/K+-ATPase cardiac signaling and contractility. Physiol Genomics 48:739-748
Gopalakrishnan, Kathirvel; Kumarasamy, Sivarajan; Mell, Blair et al. (2015) Genome-wide identification of long noncoding RNAs in rat models of cardiovascular and renal disease. Hypertension 65:200-10
Mehta, Gaurav; Kumarasamy, Sivarajan; Wu, Jian et al. (2015) MITF interacts with the SWI/SNF subunit, BRG1, to promote GATA4 expression in cardiac hypertrophy. J Mol Cell Cardiol 88:101-10

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