Single Nucleotide Polymorphism analysis of the human adenosine A2B receptor gene: prevalence of SNPs in asthmatics and normal subjects

Abstract

The adenosine A_2B receptor is found on human lung mast cells and is believed to mediate the bronchoconstriction in response to adenosine characteristic of asthmatics. As such it represents an attractive therapeutic target for asthma and allergic rhinitis. As genetic variability in drug targets may affect an individual's response to treatment, the adenosine A_2B receptor gene was analyzed for polymorphisms and their prevalence defined in a Caucasian population. The coding region of the A_2B receptor gene as well as the intron-exon boundaries of the gene were found to be free of genetic variation. Three single nucleotide polymorphisms were identified in the promoter region of the gene, one of which created a BamHI restriction fragment length polymorphism. The prevalence of the three single nucleotide polymorphisms in an unselected population was <5%. The prevalence of the BamHI polymorphism was investigated in a British population of 40 asthmatics and 40 non-asthmatics: no excess of the BamHI variant was observed in asthmatic subjects. The data indicates that any variability in drug response would likely not be due to direct structural variation of the A_2B receptor protein. Further, polymorphism at the A_2B receptor genomic locus is unlikely to contribute to the population risk of developing asthma.