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 #
5R01HL020176-35
Application #
8245047
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
OH, Youngsuk
Project Start
1988-06-01
Project End
2013-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
35
Fiscal Year
2012
Total Cost
$555,622
Indirect Cost
$184,713
Name
University of Toledo
Department
Physiology
Type
Schools of Medicine
DUNS #
807418939
City
Toledo
State
OH
Country
United States
Zip Code
43614
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
Mell, Blair; Abdul-Majeed, Shakila; Kumarasamy, Sivarajan et al. (2015) Multiple blood pressure loci with opposing blood pressure effects on rat chromosome 1 in a homologous region linked to hypertension on human chromosome 15. Hypertens Res 38:61-7
Singh, Vishal; Chassaing, Benoit; Zhang, Limin et al. (2015) Microbiota-Dependent Hepatic Lipogenesis Mediated by Stearoyl CoA Desaturase 1 (SCD1) Promotes Metabolic Syndrome in TLR5-Deficient Mice. Cell Metab 22:983-96
Mell, Blair; Jala, Venkatakrishna R; Mathew, Anna V et al. (2015) Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiol Genomics 47:187-97
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
Kumarasamy, Sivarajan; Waghulde, Harshal; Gopalakrishnan, Kathirvel et al. (2015) Mutation within the hinge region of the transcription factor Nr2f2 attenuates salt-sensitive hypertension. Nat Commun 6:6252
Joe, Bina (2015) Dr Lewis Kitchener Dahl, the Dahl rats, and the ""inconvenient truth"" about the genetics of hypertension. Hypertension 65:963-9
Aboualaiwi, Wissam A; Muntean, Brian S; Ratnam, Shobha et al. (2014) Survivin-induced abnormal ploidy contributes to cystic kidney and aneurysm formation. Circulation 129:660-72
Abdul-Majeed, Shakila; Mell, Blair; Nauli, Surya M et al. (2014) Cryptorchidism and infertility in rats with targeted disruption of the Adamts16 locus. PLoS One 9:e100967

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