The Impact of β 2 Adrenergic Receptor Polymorphisms on the Outcomes in Cardiovascular Diseases

Cardiovascular diseases (CVD) include a heterogeneous group of multifactorial conditions and represent the major health problem in the western society. Many studies have evidenced that inter-individual variability affects the prognosis and the response to pharmacological treatment in patients with CVD. The identification of genetic markers to select patients more susceptible to develop cardiovascular complications has a therapeutic interest for undertaking individualized therapeutic approach. The sympathetic nervous system acts through adrenergic receptor subtypes and plays a key role in the development and prognosis of CVD. In particular, β-2 adrenergic receptors (β₂AR), expressed in a wide variety of tissues, are critical regulators of cardiac output, peripheral vascular resistance and metabolism. Several variations with multiple single-nucleotide polymorphisms have been identified in β₂AR gene. There are 3 common β₂AR polymorphisms characterized in more detail for their influence on functional receptor activity. In particular, the changing an arginine for a glycine at position 16 of the receptor protein (Arg16Gly) is associated with increased agonist-induced down-regulation; the substitution of glutamine with glutamic acid at position 27 (Gln27Glu) leads to resistance to down-regulation; the substitution of threonine with isoleucine (Thr164Ile) at position 164 causes receptor uncoupling from the G protein. Many studies have indicated the association of β₂AR polymorphisms with various cardiovascular and metabolic diseases and have contributed to indicate the β₂AR gene variants an appropriate target for investigating possible links between receptor polymorphisms, drug responses and susceptibility to CVD. However, the reports on the association of β₂AR polymorphisms with clinical outcomes of CVD have been contradictory. In this review, we will illustrate the effects of β₂ARs genetic variability on the management of CVD.