Basic Research in Cardiology

, Volume 96, Issue 6, pp 606–611

Molecular genetics of G proteins and atherosclerosis risk

  • Winfried Siffert

DOI: 10.1007/s003950170012

Cite this article as:
Siffert, W. Basic Res Cardiol (2001) 96: 606. doi:10.1007/s003950170012


Using a classical candidate gene approach, we have described a common C825T polymorphism in the gene GNB3 which encodes the ubiquitously expressed β3 subunit of heterotrimeric G proteins. The 825T allele is associated with alternative splicing of the gene and the formation of a truncated but functionally active β3 subunit which is referred to as Gβ3s. Expression of the splice variant results in an enhanced G protein activation on stimulation of G protein-coupled receptors. Carriers of the 825T allele show an increased risk for hypertension and left ventricular hypertrophy. Homo- and heterozygous 825T allele carriers respond with a stronger decrease in blood pressure to therapy with a thiazide diuretic than homozygous 825C allele carriers. Moreover, 825T allele carriers appear to have an increased risk for obesity which appears sensible given the established role of G protein signaling in adipogenesis. The highest frequencies of the 825T allele are found in ethnicities with the highest lifestyle-dependent risk for obesity, e.g., black Africans and East Asians. This suggests that the 825T allele fulfills the criteria of a thrifty genotype.

Key words Signal transduction – hypertension – obesity – gene – polymorphism

Copyright information

© Steinkopff Verlag 2001

Authors and Affiliations

  • Winfried Siffert
    • 1
  1. 1.Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstr. 55, 45122 Essen, Germany, Tel.: +49-201/723-3470, Fax: +49-201/723-5968, E-Mail: winfried.siffert@uni-essen.deDE