Identification of novel polymorphisms within the promoter region of the human β₂ adrenergic receptor gene

Abstract

By screening the 1470 bp 5′ to the start codon of the human β2 adrenergic 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. β2 adrenergic receptor start codon). Transient transfection of 5′ flanking deletion luciferase reporter constructs demonstrated the majority of activity of the human β2 adrenergic gene 5′ 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′ 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 β2 adrenergic receptor gene expression.British Journal of Pharmacology (1999) 126, 841–844; doi:10.1038/sj.bjp.0702385

Influence of β2-adrenoceptor gene polymorphisms on β2-adrenoceptor expression in human lung

“…Polymorphisms within the promoter region of ADRB2, especially those at -47T>C (BUP-cys to BUP-arg) and -367T>C, have been associated with differences in β 2 -adrenoceptor expression in transfected cells [11][12][13][14][15]. By contrast, a study using lymphocytes isolated from asthmatics demonstrated that there was no association between the polymorphism at -47 and β 2 -adrenoceptor expression [17].…”

“…3). Position -367 within the promoter region of ADRB2 has also been linked to influencing receptor expression [12,15]. However, in human lung this position had no influence on β 2 -adrenoceptor expression ( Table 4).…”

“…Polymorphisms within the promoter region of ADRB2 have been associated with the regulation of receptor expression [11][12][13][14][15]. In particular, a polymorphism at position -47 has been strongly linked to β 2 -adrenoceptor expression [11].…”

“…BUP-arg has been reported to attenuate β 2 -adrenoceptor expression [11]. In addition to position -47, position -367 within the promoter region has also been linked to influencing receptor expression as the polymorphism (-367T>C) interrupts a potential binding site for transcription factors [12,14].…”

“…An influence of polymorphisms on β 2 -adrenoceptor expression has been assessed in transfected cells and lymphocytes with equivocal outcomes [11][12][13][14][15]17]. The aim of the present study was to perform a comprehensive analysis of the influence of polymorphisms across ADRB2 on β 2 -adrenoceptor expression in human lung tissue.…”