The significance of β2-adrenergic receptor polymorphisms in asthma

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Abstract
The gene that encodes the beta2-adrenergic receptor (ADRB2) is one of the most studied candidate genes in asthma. This review examines recent articles of the relationship between ADRB2 polymorphisms and asthma. Candidate gene association studies of ADRB2 and asthma have been dominated by analyses of the two common non-synonymous coding single nucleotide polymorphisms, Arg16Gly and Glu27Gly. Published studies have yielded inconsistent results. Three recent meta-analyses on the effects of these two polymorphisms have found no associations with asthma, although there were suggestions of associations with other asthma-related phenotypes, such as nocturnal asthma and asthma severity. Other recent studies have investigated other single nucleotide polymorphisms in this gene (i.e. single nucleotide polymorphisms in the promoter region and other single nucleotide polymorphisms in the coding region). These analyses have investigated the association between these single nucleotide polymorphisms (and haplotypes of these polymorphisms) and asthma-related phenotypes such as lung function, airways hyperresponsiveness, and response to a bronchodilator, and have suggested that certain regions of the gene may be associated with different phenotypes. Results from these studies, however, have also been inconsistent. Polymorphisms of ADRB2 are not major risk factors for the development of asthma. These polymorphisms are likely to be important, however, in determining drug response. Future studies need to fully characterize all of the variation in the gene and perform comprehensive association studies. Finally, interactions between ADRB2 and other genes in the beta-agonist pathway are an important and active area of research that will shed more light on inter-individual differences in drug response.

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