Identification of novel polymorphisms within the promoter region of the human beta(2) adrenergic receptor gene

By screening the 1470 bp 5' to the start codon of the human beta(2) adrener gic receptor gene, we have identified a total of eight polymorphisms (-20 T -->C, -47 T-->C, -367 T-->C, -468 C-->G, -654 G-->A, -1023 G-->A, -1343 A-- >G and -1429 T-->A c.f. beta(2) adrenergic receptor start codon). Transient transfection of 5' flanking deletion luciferase reporter constructs demons trated the majority of activity of the human beta(2) adrenergic gene 5' fla nking region to be present within a 549 bp fragment immediately upstream fr om the start codon. Because of linkage disequilibrium, some combinations of polymorphisms were particularly frequent. We transiently transfected COS-7 cells with luciferase constructs under the control of the 549 bp of 5' fla nking DNA containing the two most frequent extended haplotypes in this regi on. Luciferase activity was significantly reduced in cells transfected with the 'mutant' construct (-20C, -47C, -367C, 468G) c.f. the 'wild-type' cons truct (-20T, -47T, -367T, -468C). These data suggest that polymorphisms hav e the potential to alter human beta(2) adrenergic receptor gene expression.