The pharmacogenetics of asthma: a candidate gene approach

Antithetic regulation by β-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway β-agonist paradox

“…Based on the current work, these observations reflect how the trigger for the events leading to enhanced contractile responsiveness by way of β 2 AR activation can be modified. Furthermore, with the identification of this cross talk event, the genes encoding the PLC isoforms are candidates that should be interrogated for polymorphisms (28), given that there is interindividual variability in β-agonist-promoted bronchial hyperreactivity and bronchoprotection in humans. Concerning regulatory regions within the PLC gene that may be influenced by βAR activity, we are unaware of any reports of potential control motifs or transcription-binding sites.…”

Autonomic Nervous System Pharmacogenomics: A Progress Report

“…␤ 2 -Adrenergic Receptor Polymorphisms and Asthma. Numerous association studies have been carried out with respect to ␤ 2 -AR SNPs and asthma (Liggett, 2000a;Silverman et al, 2001;Fenech and Hall, 2002;Joos and Sandford, 2002;Palmer et al, 2002;Taylor and Kennedy, 2002;Small et al, 2003). Overall, the data suggest that ␤ 2 -AR polymorphisms, especially Arg16Gly, may play a role in airway hyperresponsiveness, bronchodilator sensitivity and response to ␤-agonist, long-term use of ␤-agonist, and tolerance (Table 11) Martinez et al, 1997;Tan et al, 1997;D'Amato et al, 1998;Kotani et al, 1999;Fowler et al, 2000;Israel et al, 2000;Lima et al, 2000;Taylor et al, 2000a).…”

“…The impact of the coding sequence variants of the ␤ 2 -AR has been reviewed with regard to some aspects of function and disease associations, and interested readers should consult these reviews: (Buscher et al, 1999a;Liggett, 2000a,b;Silverman et al, 2001;Fenech and Hall, 2002;Joos and Sandford, 2002;Palmer et al, 2002;Taylor and Kennedy, 2002;Wood, 2002;Small et al, 2003). We will emphasize the role of variant receptors in drug responses (especially cardiovascular responses) in vitro and in vivo.…”

International Union of Basic and Clinical Pharmacology. LXXXIV: Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions

“…Furthermore, many of the genes encoding proteins involved in the synthesis and signaling pathways of the cysteinyl LTs are polymorphic and are of interest in genetic studies of asthma (Silverman et al, 2001;Palmer et al, 2002;Israel, 2005).…”