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Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation

Item Type:Article
Title:Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation
Creators Name:Funke-Kaiser, H. and Reichenberger, F. and Koepke, K. and Herrmann, S.M. and Pfeifer, J. and Orzechowski, H.D. and Zidek, W. and Paul, M. and Brand, E.
Abstract:The endothelin-converting enzyme (ECE)-1 gene is a candidate for human blood pressure (BP) regulation and we report the identification of the new gene variants T-839G, C-338A, L75F, A677V and C+295T. Transient transfection of the reporter constructs containing the -338A allele showed an increase in promoter activity compared with the wild-type promoter. EMSA revealed the specific binding of E2F-2 to both ECE-1b promoter sequences, with the -338A allele being associated with an increased affinity to E2F-2 compared with -338C. The clinical relevance of this finding was analyzed in 704 hypertensive patients. In untreated hypertensive women, both the -338A and -839G alleles were significantly associated with ambulatory BP values. This study provides the first evidence of a link between the cell-cycle-associated E2F family and BP regulation via a component of the endothelin system.
Keywords:Alleles, Aspartic Endopeptidases, Blood Pressure, Cultured Cells, Molecular Cloning, DNA, E2F2 Transcription Factor, Reporter Genes, Genotype, Haplotypes, Hypertension, Linkage Disequilibrium, Metalloendopeptidases, Genetic Polymorphism, Promoter Regions, Protein Binding, Time Factors, Transcription Factors, Transfection
Source:Human Molecular Genetics
ISSN:0964-6906
Publisher:Oxford University Press (U.K.)
Volume:12
Number:4
Page Range:423-433
Date:15 February 2003
Official Publication:http://hmg.oxfordjournals.org/cgi/content/abstract/12/4/423
PubMed:View item in PubMed

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