title: Beta 2 adrenergic receptor 5' haplotypes influence promoter activity.
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.
authors.affiliation: Human Genetics Center, University of Texas School of Public Health, 1200 Herman Pressley RAS E477, Houston, TX 77030, U.S.A.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Johnatty
authors.forename: Maha
authors.initials: M
authors.lastname: Abdellatif
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shimmin
authors.forename: Richard B
authors.initials: RB
authors.lastname: Clark
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
mesh_terms: D002460:Cell Line; D006239:Haplotypes / Q000502:physiology*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011110:Polymorphism, Genetic / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000502:physiology*; D018709:Statistics, Nonparametric; D014162:Transfection / Q000379:methods
chemical_list: D018343:Receptors, Adrenergic, beta-2; D008156:Luciferases