Alterations in the regulation of adenylyl cyclase (ADCY) activity in G protein-coupled receptor signaling have been implicated in the pathogenesis of hypertension, heart failure, and diabetes; however, the importance of genetic variability has been underappreciated. Hodges et al. investigated the association between expression of an ADCY genetic variant [specifically adenylyl cyclase 6 (A674S: ADCY6 A674S)] and specific cardiovascular phenotypic characteristics in healthy volunteers. The occurrence of the ADCY6 A674S genetic variant, a known hyperactive form of ADCY, was approximately 7% in whites. Expression of the genetic variant was associated with increased blood pressure and hyperdynamic cardiovascular responses under baseline conditions and in response to stressors that activate ADCY. In addition, an alteration in the distribution of body fat was observed. The pronounced vasodilator response to handgrip exercise observed in the ADCY6 variant group supports the hyperfunctional state of this genetic variant. These studies suggest that genetic variation seen in ADCY and its activation state may be important determinants of human cardiovascular function and may have implications pertaining to the development of cardiovascular disease and/or complications related to certain metabolic disorders.
See article at J Pharmacol Exp Ther 2010, 335:451–457.
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