Premium
β 2 adrenergic receptor 5′ haplotypes influence promoter activity
Author(s) -
Johnatty Sharon E,
Abdellatif Maha,
Shimmin Lawrence,
Clark Richard B,
Boerwinkle Eric
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704935
Subject(s) - haplotype , luciferase , mutant , receptor , biology , microbiology and biotechnology , transfection , genetics , gene , promoter , single nucleotide polymorphism , allele , genotype , gene expression
Transcriptional control of the human β 2 adrenergic receptor gene (ADRB2) predominantly resides within a 549 base pair region immediately 5′ to the start of translation. Within this region, four naturally occurring polymorphisms, −468 C→G, −367 T→C, −47 T→C, and −20 T→C, have been identified. To determine the individual site and haplotype effects of these polymorphisms, we generated 16 luciferase‐based mutant constructs which were transiently transfected into HEK293 cells, and measured ADRB2 promoter‐driven luciferase activity. Two of the 16 mutant constructs, GCCT (−468G, −367C, −47C, −20T) and CTCT, showed a highly significant 3 fold decrease in luciferase induction relative to the reference CTTT. These haplotype effects could not be accounted for by the separate and additive effects of each site. These findings indicate that promoter polymorphisms interact to significantly alter β 2 adrenergic receptor expression, and should be examined further for their association with disease‐related phenotypes.British Journal of Pharmacology (2002) 137 , 1213–1216. doi: 10.1038/sj.bjp.0704935