Essential hypertension is a multifactorial disorder with a Gaussian distribution and with a genetic component that appears to be polygenic and heterogeneous. The purpose of this project is to seek out genes or genetic markers which identify subjects more vulnerable to hypertension under the influence of environmental factors. The studies require clinical knowledge of the pathophysiology and therapy of hypertension, availability of a large racially diverse patient population and a General Clinical Research Center for recruitment, characterization and classification of subjects, in combination with knowledge of molecular biology for DNA preparation and expertise in molecular genetics and molecular epidemiology for genetic analysis. The five Specific Aims of this project are: 1) To classify hypertensives into relatively homogeneous subgroups according to intermediate phenotypes based on heritable biological traits, including anthropometric and neurohumoral data obtained by submitting selected subjects to a 3-day inpatient protocol, from which data may be extrapolated and applied to stratify larger subject populations in order to enhance efficacy of subsequent genetic analysis; 2) To genotype subjects for chromosomal loci using approximately 350 highly polymorphic microsatellite markers spaced every 5-10 cM along each chromosome. The strategy is to initially type markers in a select group of hypertensive kindreds that can independently demonstrate linkage; 3) To analyze the genetic marker data for linkage using both parametric (lod score) and nonparametric (affected-pedigree-member) methods. Suggestive findings will be pursued in the sib-pairs; 4) Case-control studies will be used to confirm positive linkage from aim 3 and to identify particular allele associations using methods of linkage disequilibrium and DNA pooling; 5) To screen and assess mutations in candidate genes linked to hypertension in patients and controls.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL055001-04
Application #
6110553
Study Section
Project Start
1999-02-01
Project End
2000-01-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Boston University
Department
Type
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Duka, Arvi; Schwartz, Faina; Duka, Irena et al. (2006) A novel gene (Cmya3) induced in the heart by angiotensin II-dependent but not salt-dependent hypertension in mice. Am J Hypertens 19:275-81
Shenouda, Sherene M; Johns, Conrado; Kintsurashvili, Ekaterina et al. (2006) Long-term inhibition of the central alpha(2B)-adrenergic receptor gene via recombinant AAV-delivered antisense in hypertensive rats. Am J Hypertens 19:1135-43
Cardoso de Carvalho, Fabio; Bregagnollo, Edson; Santos Silva, Vanessa et al. (2006) Frequency of coronary artery disease in patients with renal artery stenosis without clinical manifestations of coronary insufficiency. Am J Hypertens 19:1125-8
Cui, Jing; Melista, Efthymia; Chazaro, Irmarie et al. (2005) Sequence variation of bradykinin receptors B1 and B2 and association with hypertension. J Hypertens 23:55-62
Manolis, Athanasios J; Iraklianou, Stella; Pittaras, Andreas et al. (2005) Arterial compliance changes in diabetic normotensive patients after angiotensin-converting enzyme inhibition therapy. Am J Hypertens 18:18-22
Ignjacev-Lazich, Ivana; Kintsurashvili, Ekaterina; Johns, Conrado et al. (2005) Angiotensin-converting enzyme regulates bradykinin receptor gene expression. Am J Physiol Heart Circ Physiol 289:H1814-20
Russo, Christopher J; Melista, Efthymia; Cui, Jing et al. (2005) Association of NEDD4L ubiquitin ligase with essential hypertension. Hypertension 46:488-91
Schwartz, Faina; Duka, Arvi; Duka, Irena et al. (2004) Novel targets of ANG II regulation in mouse heart identified by serial analysis of gene expression. Am J Physiol Heart Circ Physiol 287:H1957-66
Elijovich, Fernando; Laffer, Cheryl L; Schiffrin, Ernesto L et al. (2004) Endothelin-aldosterone interaction and proteinuria in low-renin hypertension. J Hypertens 22:573-82
Erlich, Porat M; Cui, Jing; Chazaro, Irmarie et al. (2003) Genetic variants of WNK4 in whites and African Americans with hypertension. Hypertension 41:1191-5

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