Pharmacogenomics of G Protein-Coupled Receptor Ligands in Cardiovascular Medicine

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

“…Although several gene polymorphisms have been reported in the AT1R and other components of the RAAS, they have not consistently been associated with altered drug responses to ARBs (Rosskopf and Michel, 2008). However, polymorphisms of drug metabolizing enzymes and, perhaps more importantly, drug transporters may affect the pharmacokinetics of several ARBs.…”

Polymorphic Variants of Adrenoceptors: Pharmacology, Physiology, and Role in Disease

“…In addition to other factors, genetic heterogeneity of adrenoceptor genes among patients is suggested as a possible underlying cause for the variation of therapeutic efficacy when using these agents (Rosskopf and Michel, 2008).…”

Identification of a novel 12-nucleotide insertion polymorphism in the promoter region of ADRA2B: Full linkage with the 9-nucleotide deletion in the coding region and influence on transcriptional activity

“…The upper band, which exhibits the same relative mobility but much stronger signal intensity than that found with the ADRA2B-del probe, likely corresponds to the same complex as band A and was therefore termed A'. As [4,18]. The +901 Del polymorphism has, however, been associated with exaggerated coronary constriction in response to adrenaline infusion [19].…”

“…Hence the Del 2B -AR variant is expected to exhibit enhanced function. Clinical trials and epidemiologic studies investigating the consequences of the +901 Del variation on vascular responses to 2 -agonist administration [4] or its possible association with cardiovascular diseases [5] have, however, yielded inconsistent results. Examination of a 5.8 kb genomic fragment comprising 2.2 kb upstream and 2.3 kb downstream from the coding sequence demonstrated the existence of several single nucleotide polymorphisms (SNPs) in different regions of the ADRA2B gene [6][7][8].…”