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

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...

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Bibliographic Details
Published in:Human molecular genetics 2003-02, Vol.12 (4), p.423-433
Main Authors: Funke-Kaiser, Heiko, Reichenberger, Florian, Köpke, Karla, Herrmann, Stefan-Martin, Pfeifer, Jacqueline, Orzechowski, Hans-Dieter, Zidek, Walter, Paul, Martin, Brand, Eva
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
Aspartic Acid Endopeptidases - genetics
Aspartic Acid Endopeptidases - metabolism
Biological and medical sciences
Blood Pressure
Cells, Cultured
Cloning, Molecular
DNA - metabolism
E2F2 Transcription Factor
Endothelin-Converting Enzymes
Female
Fundamental and applied biological sciences. Psychology
Gene expression
Genes, Reporter
Genotype
Haplotypes
Humans
Hypertension - metabolism
Linkage Disequilibrium
Male
Metalloendopeptidases
Middle Aged
Molecular and cellular biology
Molecular genetics
Polymorphism, Genetic
Promoter Regions, Genetic
Protein Binding
Time Factors
Transcription Factors - genetics
Transcription Factors - metabolism
Transfection
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Summary: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.
ISSN:0964-6906
1460-2083
1460-2083
DOI:10.1093/hmg/ddg040