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

By screening the 1470 bp 5 theta to the start codon of the human beta sub(2) adrenergic receptor gene, we have identified a total of eight polymorphisms (-20 T arrow right C, -47 T arrow right C, -367 T arrow right C, -468 C arrow right G, -654 G arrow right A, -1023 G arrow right A, -1343 A arrow right G and -1429 T arrow right A c.f. beta sub(2) adrenergic receptor start codon). Transient transfection of 5 theta flanking deletion luciferase reporter constructs demonstrated the majority of activity of the human beta sub(2) adrenergic gene 5 theta flanking region to be present within a 549 bp fragment immediately upstream from 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 theta flanking DNA containing the two most frequent extended haplotypes in this region. Luciferase activity was significantly reduced in cells transfected with the `mutant' construct (-20C, -47C, -367C, -468G) c.f. the `wild-type' construct (-20T, -47T, -367T, -468C). These data suggest that polymorphisms have the potential to alter human beta sub(2) adrenergic receptor gene expression.