SNPs in genes encoding G proteins in pharmacogenetics

Abstract

Heterotrimeric guanine-binding proteins (G proteins) transmit signals from the cell surface to intracellular signal cascades and are involved in various physiological and pathophysiological processes. Polymorphisms in the genes GNB3 (encoding the Gβ3 subunit), GNAS (encoding the Gαs subunit) and GNAQ (encoding the Gαq subunit) have been the primary focus of investigation. Polymorphisms in these genes could be associated with different complex phenotypes underlining that alterations in G-protein signaling can cause multiple disorders. G proteins present a point of convergence or ‘bottleneck’ between various receptors and effectors, thus making them a sensible tool for pharmacogenetic studies. The pharmacogenetic studies performed to date mostly demonstrate an association between G-protein polymorphisms and response to therapy or occurrence of adverse drug effects. Therefore, polymorphisms in genes encoding G-protein subunits may help to individualize drug treatment in various diseases with regard to both efficacy and safety.