Beta 2 adrenergic receptor 5' haplotypes influence promoter activity.

TitleBeta 2 adrenergic receptor 5' haplotypes influence promoter activity.
Publication TypeJournal Article
Year of Publication2002
AuthorsJohnatty, SE, Abdellatif, M, Shimmin, L, Clark, RB, Boerwinkle, E
JournalBr J Pharmacol
Volume137
Issue8
Pagination1213-6
Date Published2002 Dec
ISSN0007-1188
KeywordsCell Line, Haplotypes, Humans, Luciferases, Mutation, Polymorphism, Genetic, Promoter Regions, Genetic, Receptors, Adrenergic, beta-2, Statistics, Nonparametric, Transfection
Abstract

1. Transcriptional control of the human beta(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. 2. 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. 3. 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. 4. These findings indicate that promoter polymorphisms interact to significantly alter beta(2) adrenergic receptor expression, and should be examined further for their association with disease-related phenotypes.

DOI10.1038/sj.bjp.0704935
Alternate JournalBr. J. Pharmacol.
PubMed ID12466230
PubMed Central IDPMC1573596