(Hypertension. 2000;35:164.)
© 2000 American Heart Association, Inc.
State-of-the-Art Lectures |
Genes and Hypertension
From Gene Mapping in Experimental Models to Vascular Gene Transfer Strategies
From the BHF Blood Pressure Group, Department of Medicine and Therapeutics, University of Glasgow, Scotland.
Correspondence to Prof Anna F. Dominiczak, BHF Blood Pressure Group, Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland. E-mail: ad7e{at}clinmed.gla.ac.uk
Abstract—Human essential hypertension is a complex, multifactorial, quantitative trait under a polygenic control. Several strategies have been developed over the last decade to dissect genetic determinants of hypertension. Of these, the most successful have been studies that identified rare mendelian syndromes in which a single gene mutation causes high blood pressure. The attempts to identify multiple genes, each with a small contribution to the common polygenic form of hypertension, have been less successful. Several laboratories focused their attention on rat models of genetic hypertension, which can be considered as a reductionist paradigm for human disease. Using numerous crosses between hypertensive and normotensive strains, investigators identified several quantitative trait loci (QTL) for blood pressure subphenotypes and for cardiovascular complications such as left ventricular hypertrophy, kidney failure, stroke, and insulin resistance. Furthermore, congenic strains have been produced to confirm the existence of some of these QTL and to narrow down the chromosomal regions of interest. A number of interesting strategies have been developed, including a "speed" congenic strategy perfected by our group in Glasgow. However, the limit of congenic strategy is estimated at 1 cM, which corresponds to 2x106 base pairs of DNA and 
50 candidate genes. It is envisaged that gene expression profiling with cDNA microarrays might allow a quick progression toward the gene identification within cardiovascular QTL. In parallel experimental effort, several laboratories have been developing gene transfer/therapy strategies with adenoviral or adeno-associated viral vectors used, for example, to overexpress protective vascular genes such as vascular endothelial growth factor or endothelial nitric oxide synthase. It is anticipated that further developments in positional cloning of susceptibility and severity genes in hypertension and its complications will lead to a direct transfer of these discoveries to essential hypertension in humans and will ultimately produce novel targets for local and systemic gene therapy in cardiovascular disease.
Key Words: genes • rats • stroke • endothelium • hypertension, essential
This article has been cited by other articles:
 |
|
 |
|
  T. Nakayama, N. Kuroi, M. Sano, Y. Tabara, T. Katsuya, T. Ogihara, Y. Makita, A. Hata, M. Yamada, N. Takahashi, et al. Mutation of the Follicle-Stimulating Hormone Receptor Gene 5'-Untranslated Region Associated With Female Hypertension Hypertension, September 1, 2006; 48(3): 512 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Racasan, B. Braam, H. A. Koomans, and J. A. Joles Programming blood pressure in adult SHR by shifting perinatal balance of NO and reactive oxygen species toward NO: the inverted Barker phenomenon Am J Physiol Renal Physiol, April 1, 2005; 288(4): F626 - F636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. McBride, M. J. Brosnan, J. Mathers, L. I. McLellan, W. H. Miller, D. Graham, N. Hanlon, C. A. Hamilton, J. M. Polke, W. K. Lee, et al. Reduction of Gstm1 Expression in the Stroke-Prone Spontaneously Hypertension Rat Contributes to Increased Oxidative Stress Hypertension, April 1, 2005; 45(4): 786 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Dominiczak, D. Graham, M. W. McBride, N. J.R. Brain, W. K. Lee, F. J. Charchar, M. Tomaszewski, C. Delles, and C. A. Hamilton Cardiovascular Genomics and Oxidative Stress Hypertension, April 1, 2005; 45(4): 636 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nakagawa, J. S. Marji, M. L. Schwartzman, M. R. Waterman, and J. H. Capdevila Androgen-mediated induction of the kidney arachidonate hydroxylases is associated with the development of hypertension Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R1055 - R1062. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Alemayehu, L. Breen, D. Krenova, and M. P. Printz Reciprocal rat chromosome 2 congenic strains reveal contrasting blood pressure and heart rate QTL Physiol Genomics, September 3, 2002; 10(3): 199 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. R. Holla, F. Adas, J. D. Imig, X. Zhao, E. Price Jr., N. Olsen, W. J. Kovacs, M. A. Magnuson, D. S. Keeney, M. D. Breyer, et al. Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause hypertension PNAS, April 24, 2001; 98(9): 5211 - 5216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. SAAD, M. R. GARRETT, and J. P. RAPP Multiple blood pressure QTL on rat chromosome 1 defined by Dahl rat congenic strains Physiol Genomics, January 19, 2001; 4(3): 201 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Provoost, M. Shiozawa, R. P. E. Van Dokkum, and H. J. Jacob Transfer of the Rf-1 region from FHH onto the ACI background increases susceptibility to renal impairment Physiol Genomics, February 28, 2002; 8(2): 123 - 129. [Abstract] [Full Text] [PDF]
|
|