Polymorphism of beta 2-adrenergic receptors

• Published in: Wiadomości lekarskie (1960) Vol. 56; no. 5-6; p. 283
• Main Authors: Weglarz, Ludmiła, Grzanka, Alicja, Kierot, Jolanta, Wilczok, Tadeusz
• Format: Journal Article
• Language: Polish
• Published: Poland 2003
• Subjects: Adrenergic beta-Agonists - therapeutic use; Amino Acid Sequence; Asthma - drug therapy; Asthma - genetics; Down-Regulation; Humans; Molecular Sequence Data; Polymorphism, Genetic - genetics; Receptors, Adrenergic, beta-2 - chemistry; Receptors, Adrenergic, beta-2 - drug effects; Receptors, Adrenergic, beta-2 - genetics
• ISSN: 0043-5147

The human beta 2-adrenoceptor is a member of the seven-transmembrane family of receptors. It is expressed in many cell types such as airway smooth muscle cells, neutrophils, eosinophiles, alveolar macrophages and airway epithelial cells. The beta 2-adrenoceptor agonists are the most important group of bronchodilator drugs used in the treatment of asthma. They are classified by their selectivity, affinity for the receptor, potency and pharmacological efficacy. The gene encoding the beta 2-adrenergic receptor is highly polymorphic in the human population. Polymorphism affecting amino acids 16, 27 and 164 are the most common and they have been shown to correlate with some clinical features of asthma, including airways reactivity. They can modulate the behaviour of the beta 2-receptor, altering ligand binding and the characteristics of down-regulation following agonist exposure. The homozygous glycine-16 (Arg-->Gly) variant of the beta 2-adrenoceptor is known to predispose to agonist-induced down-regulation and desensitization, and may play a role in the pathogenesis of asthma severity. The polymorphism at position 27 (Gln-->Glu) is associated with decreased airway responsiveness. The polymorphic variant 164 (Thr-->Ile) shows impaired agonist binding and decreased adenylyl cyclase activity. No convincing evidence has been presented demonstrating a linking of asthma per se with this receptor polymorphism.