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Association of a human G-protein β3 subunit variant with hypertension

Nature Genetics volume 18, pages 45–48 (1998)Cite this article

Abstract

Hypertension is a common disorder of multifactorial origin that constitutes a major risk factor for cardiovascular events such as stroke and myocardial infarction. Previous studies demonstrated an enhanced signal transduction via pertussis toxin-sensitive G proteins in lymphoblasts and fibroblasts from selected patients with essential hypertension. We have detected a novel polymorphism (C825T) in exon 10 of the gene encoding the p3 subunit of heterotrimeric G proteins (GNB3). The T allele is associated with the occurrence of a splice variant, GNB3–S (encoding Gβ3–s), in which the nucleotides 498–620 of exon 9 are deleted. This in-frame deletion causes the loss of 41 amino acids and one WD repeat domain of the Gβ subunit. By western-blot analysis, Gβ3–s appears to be predominantly expressed in cells from individuals carrying the T allele. Significant enhancement of stimulated GTPγS binding to Sf9 insect cells expressing Gβ3–s together with Ga 2 and Gy5 indicates that this splice variant is biologically active. Genotype analysis of 427 normotensive and 426 hypertensive subjects suggests a significant association of the T allele with essential hypertension.

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Authors and Affiliations

  1. Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse. 55, D-45122, Essen, Germany

    Winfried Siffert, Dieter Rosskopf, Gerlinde Siffert, Stefan Busch, Albrecht Moritz & Karl H. Jakobs

  2. Abteilung für Kardiologie, Universitätsklinikum Essen, D-45122, Essen, Germany

    Raimund Erbel

  3. Universitätsklinikum Benjamin Franklin, Abteilung für Endokrinologie und Nephrologie, D-12200, Berlin, Germany

    Arya M. Sharma

  4. Klinikum der Universität Heidelberg, Sektion Nephrologie, D-69115, Heidelberg, Germany

    Eberhard Ritz

  5. GSF–Forschungszentrumfür Umwelt und Gesundheit, Institut für Epidemiologie, D-85764, Neuherberg, Germany

    H.-Erich Wichmann

  6. Institutfür Humangenetik, Universitätsklinikum Essen, D-45122, Essen, Germany

    Bernhard Horsthemke

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  1. Winfried Siffert
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Correspondence to Winfried Siffert.

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Siffert, W., Rosskopf, D., Siffert, G. et al. Association of a human G-protein β3 subunit variant with hypertension. Nat Genet 18, 45–48 (1998). https://doi.org/10.1038/ng0198-45

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