Stephane Schaak, Jeanne Mialet-Perez, Christodoulos Flordellis and Herve Paris Pages 217 - 231 ( 15 )
Adrenergic receptors (ARs) are directly or indirectly involved in the control of a large panel of physiological functions and are the targets of drugs for the treatment of several common diseases including congestive heart failure, asthma or benign prostatic hyperplasia. The genotyping of human populations with diverse ethnicity has revealed that the genes encoding α1A-, α1B-, α2A-, α2B-, α2C-, β1-, β2- and β3-AR are polymorphic in their coding region as well as in their regulatory domains and non-coding regions. The functional consequences of these genetic variations include changes in expression at transcriptional or translational level, modification of coupling to heterotrimeric G-proteins resulting in a gain or a loss in function, and alteration of GRK-mediated receptor phosphorylation/desensitization or of agonist-promoted down-regulation. None of the mutations identified so far is per se a major risk factor for acquired or inherited disease; however, variants of α2C-AR and β1-AR may act in synergy to determine the progression of heart failure and certain combinations of polymorphisms on β2-AR correlate with asthmatic phenotypes or response to β2-agonist therapy. Herein we summarize the present knowledge on AR gene polymorphisms, and discuss the putative consequences of variations resulting in receptor malfunction on pharmacogenomics and disease predisposition.
G-Protein coupled receptor, Single nucleotide polymorphism, Mitogen activated protein kinase, Restriction fragment length polymorphism (RFLP), Inositol phosphate
INSERM, U388, Institut Louis Bugnard, CHU Rangueil, BP 84225, 31432 Toulouse Cedex 4, France.