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Science 3 May 1996:
Vol. 272. no. 5262, pp. 676 - 680
DOI: 10.1126/science.272.5262.676
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Articles

Molecular Genetics of Human Blood Pressure Variation

Richard P. Lifton

Hypertension is a common multifactorial vascular disorder of largely unknown cause. Recognition that hypertension is in part genetically determined has motivated studies to identify mutations that confer susceptibility. Thus far, mutations in at least 10 genes have been shown to alter blood pressure; most of these are rare mutations imparting large quantitative effects that either raise or lower blood pressure. These mutations alter blood pressure through a common pathway, changing salt and water reabsorption in the kidney. These findings demonstrate the utility of molecular genetic approaches to the understanding of blood pressure variation and may provide insight into the physiologic mechanisms underlying common forms of hypertension.

The author is in the Howard Hughes Medical Institute and Boyer Center for Molecular Medicine, Departments of Medicine and Genetics, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA.


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The renal tubular Na-Cl co-transporter (NCCT): a potential genetic link between blood pressure and bone density?.
D. N. Cruz (2001)
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Association Analysis of {beta}2-Adrenergic Receptor Polymorphisms With Hypertension in Japanese.
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Comparative Roles of the Renal Apical Sodium Transport Systems in Blood Pressure Control.
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E. Donnadieu, W. O. Cookson, M.-H. Jouvin, and J.-P. Kinet (2000)
J. Immunol. 165, 3917-3922
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Mutations in the Chloride Channel Gene CLCNKB as a Cause of Classic Bartter Syndrome.
M. KONRAD, M. VOLLMER, H. H. LEMMINK, L. P. W. J. VAN DEN HEUVEL, N. JECK, R. VARGAS-POUSSOU, A. LAKINGS, R. RUF, G. DESCHÊNES, C. ANTIGNAC, et al. (2000)
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   Abstract »    Full Text »    PDF »
Genome Scan for Blood Pressure Loci in Mice.
F. A. Wright, D. T. O'Connor, E. Roberts, G. Kutey, C. C. Berry, L. U. Yoneda, D. Timberlake, and G. Schlager (1999)
Hypertension 34, 625-630
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Congenic Substitution Mapping Excludes Sa as a Candidate Gene Locus for a Blood Pressure Quantitative Trait Locus on Rat Chromosome 1.
N. Hubner, Y.-A. Lee, K. Lindpaintner, D. Ganten, and R. Kreutz (1999)
Hypertension 34, 643-648
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The Role of {alpha}-Adducin Polymorphism in Blood Pressure and Sodium Handling Regulation May Not Be Excluded by a Negative Association Study.
N. Glorioso, P. Manunta, F. Filigheddu, C. Troffa, P. Stella, C. Barlassina, C. Lombardi, A. Soro, F. Dettori, P. P. Parpaglia, et al. (1999)
Hypertension 34, 649-654
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Number of Subunits Comprising the Epithelial Sodium Channel.
S. Eskandari, P. M. Snyder, M. Kreman, G. A. Zampighi, M. J. Welsh, and E. M. Wright (1999)
J. Biol. Chem. 274, 27281-27286
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Low-Renin and Nonmodulating Essential Hypertension.
D. G. Warnock (1999)
Hypertension 34, 395-397
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Angiotensinogen Gene Polymorphism Near Transcription Start Site and Blood Pressure : Role of a T-to-C Transition at Intron I.
T. Ishigami, K. Tamura, T. Fujita, I. Kobayashi, K. Hibi, M. Kihara, Y. Toya, H. Ochiai, and S. Umemura (1999)
Hypertension 34, 430-434
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Evidence for Linkage Between Essential Hypertension and a Putative Locus on Human Chromosome 17.
J. Baima, M. Nicolaou, F. Schwartz, A. L. DeStefano, A. Manolis, I. Gavras, C. Laffer, F. Elijovich, L. Farrer, C. T. Baldwin, et al. (1999)
Hypertension 34, 4-7
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A Novel Mechanism of Ion Homeostasis and Salt Tolerance in Yeast: the Hal4 and Hal5 Protein Kinases Modulate the Trk1-Trk2 Potassium Transporter.
J. M. Mulet, M. P. Leube, S. J. Kron, G. Rios, G. R. Fink, and R. Serrano (1999)
Mol. Cell. Biol. 19, 3328-3337
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To salt, or not to salt?.
T. A. Kotchen (1999)
Am J Physiol Heart Circ Physiol 276, H1807-H1808
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Glucocorticoid Induction of Epithelial Sodium Channel Expression in Lung and Renal Epithelia Occurs via trans-Activation of a Hormone Response Element in the 5'-Flanking Region of the Human Epithelial Sodium Channel alpha  Subunit Gene.
R. Sayegh, S. D. Auerbach, X. Li, R. W. Loftus, R. F. Husted, J. B. Stokes, and C. P. Thomas (1999)
J. Biol. Chem. 274, 12431-12437
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Linkage analysis of glucocorticoid and beta 2-adrenergic receptor genes with blood pressure and body mass index.
S. Takami, Z. Y. H. Wong, M. Stebbing, and S. B. Harrap (1999)
Am J Physiol Heart Circ Physiol 276, H1379-H1384
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Lack of Evidence for Association Between the Endothelial Nitric Oxide Synthase Gene and Hypertension.
N. Kato, T. Sugiyama, H. Morita, T. Nabika, H. Kurihara, Y. Yamori, and Y. Yazaki (1999)
Hypertension 33, 933-936
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Molecular advances in cardiac and cardiovascular disease.
A. Basile-Borgia, J. H Abel, and H. Mahloogi (1999)
Perfusion 14, 89-99
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