title: Association of a human G-protein beta3 subunit variant with hypertension.
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 beta3 subunit of heterotrimeric G proteins (GNB3). The T allele is associated with the occurrence of a splice variant, GNB3-s (encoding G beta3-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 G beta subunit. By western-blot analysis, G beta3-s appears to be predominantly expressed in cells from individuals carrying the T allele. Significant enhancement of stimulated GTPgammaS binding to Sf9 insect cells expressing G beta3-s together with G alpha(i)2 and G gamma5 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.
authors.affiliation: Institut für Pharmakologie, Universitätsklinikum Essen, Germany. winfried.siffert@uni-essen.de
authors.forename: W
authors.initials: W
authors.lastname: Siffert
authors.forename: D
authors.initials: D
authors.lastname: Rosskopf
authors.forename: G
authors.initials: G
authors.lastname: Siffert
authors.forename: S
authors.initials: S
authors.lastname: Busch
authors.forename: A
authors.initials: A
authors.lastname: Moritz
authors.forename: R
authors.initials: R
authors.lastname: Erbel
authors.forename: A M
authors.initials: AM
authors.lastname: Sharma
authors.forename: E
authors.initials: E
authors.lastname: Ritz
authors.forename: H E
authors.initials: HE
authors.lastname: Wichmann
authors.forename: K H
authors.initials: KH
authors.lastname: Jakobs
authors.forename: B
authors.initials: B
authors.lastname: Horsthemke
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera / Q000166:cytology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C084070:Mas7 protein, synthetic; D010455:Peptides; D011993:Recombinant Fusion Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins