Association of a human G-protein beta3 subunit variant with hypertension

Nat Genet. 1998 Jan;18(1):45-8. doi: 10.1038/ng0198-45.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Genetic Variation*
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Humans
  • Hypertension / genetics*
  • Hypertension / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Peptides / metabolism
  • Peptides / pharmacology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Spodoptera / cytology


  • Intercellular Signaling Peptides and Proteins
  • Mas7 protein, synthetic
  • Peptides
  • Recombinant Fusion Proteins
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • GTP-Binding Proteins