Coding block and 5 leader cistron polymorphisms of the beta2-adrenergic receptor.

The gene encoding the beta2-adrenergic receptor (beta2AR) is highly polymorphic in the human population. Common polymorphisms in the receptor coding block (amino acids 16 and 27) affect agonist-promoted downregulation. Another common polymorphism in the 5' leader cistron of the beta2AR gene also regulates receptor expression, but does so through a mechanism that is independent of agonist exposure. None of these polymorphisms appears to be causative factor for asthma. However, data from several studies now indicate that the asthmatic phenotype and therapeutic response may be modified by the different polymorphic variants. This modifying effect is not likely due to a single dominant polymorphic locus, but rather the result of interaction among multiple polymorphic loci that regulate receptor expression through different mechanisms.