β2-Adrenoreceptor Polymorphisms in Asthmatic Patients.

β2-adrenergic receptors (β2AR) are GTP-binding protein (G-protein) coupled receptors widely distributed in human tissue. Inhaled β2-agonist drugs exert their primary effect on the β2AR of bronchial smooth muscles, causing relaxation and bronchial dilatation. Polymorphisms in the β2AR gene have been identified, which may affect responsiveness to β2-agonists and disease severity in asthmatics. Nine single nucleotide polymorphisms (SNPs) within the coding region and eight SNPs within in the 5' upstream region of the β2AR gene have been identified. The two most studied polymorphisms are mutations in the coding region at codon 16, Arg to Gly (Arg16Gly) and at codon 27, Gln to Glu (Gln27Glu). Evidence suggests that carriers of Gly16, as well as carriers of Gln27, are prone to down-regulation of β2AR. Patients who are homozygous for Arg16 and/or Glu 27 may be more susceptible to tachyplaxis with chronic use of β2-agonists. Although β2AR polymorphism is not related to the severity of asthma, patients with nocturnal asthma have higher frequency of Gly16. A polymorphism in the 5' upstream region, 5' leader cistron (5'LC), encodes for a protein that regulates mRNA transcription. The Cys19 polymorphism in the 5'LC is associated with higher expression of β2AR. More recent studies have focused on combinations of polymorphisms across the gene region (haplotypes). The interaction of multiple SNPs within a haplotype may control β2AR function resulting in different phenotypic response in patients with asthma. β2AR polymorphism may have a significant implication in the pathophysiology of asthma and therapeutic response.