Cardiovascular pharmacogenetics: on the way toward individually tailored drug therapy.
G proteins are important mediators of hormone action in all cells of the human body. Therefore, functional polymorphisms in genes encoding G protein subunits are expected to have a marked influence upon cell activation and cardiovascular responses to hormones and drugs. The 825T allele of a common C825T polymorphism in the gene, GNB3, encoding the G beta 3 subunit, was found to be associated with increased intracellular signal transduction via G protein-coupled receptors. Originally defined as a candidate gene associated with an increased risk for essential hypertension, the 825T allele turns out to be an interesting marker in cardiovascular pharmacogenetics. Carriers of the 825T allele show an increased vasoconstriction in the skin microcirculation in response to noradrenaline, angiotensin II, and endothelin I. Coronary vasoconstriction is enhanced in 825T allele carriers in response to azepexol. On the other hand, some drugs like hydrochlorothiazide, clonidine, and endothelin receptor antagonist evoke increased effects in 825T allele carriers. It appears that the GNB3 C825T polymorphism could be an attractive marker to discriminate responders and nonresponders and might, therefore, represent an excellent candidate gene in cardiovascular pharmacogenetics.
Siffert
Winfried
W
Institut für Pharmakologie, Universitätsklinikum Essen, Essen, Germany. winfried.Siffert@uni-essen.de
D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000235:genetics*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics / Q000639:trends*; D020641:Polymorphism, Single Nucleotide
C454420:G-protein beta3 subunit; D020962:Heterotrimeric GTP-Binding Proteins