The human G-protein β3 subunit C825T polymorphism is associated with coronary artery vasoconstriction

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Abstract
Aims Abnormal coronary vasomotion plays a role in the clinical expression of coronary artery disease. We hypothesized that the functional C825T polymorphism located in the ubiquitous G-protein β3 subunit, implicated in the cellular signal transduction of many receptors, could modify artery coronary vasomotion. We assessed the potential association of the pertussis toxin-sensitive G protein β3 subunit (GNB3) gene C825T polymorphism on coronary vasomotion in humans. Methods and Results We examined the response of angiographically normal human coronary arteries (n=131) after intravenous injection of methylergonovine maleate, a vasoconstrictor, followed by injection of isosorbide dinitrate, a vasodilator, according to GNB3 genotypes. Coronary vasomotion was assessed with quantitative coronary angiography. Subjects bearing at least one T allele had greater susceptibility to vasoconstriction in response to methylergonovine maleate than CC subjects, whereas vasodilation in response to isosorbide dinitrate did not differ among the different genotypes. Conclusion The C825T polymorphism of the G-protein β3 subunit may be a genetic determinant of coronary artery vasomotion in humans.

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