Journal Article

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

Heiko Funke-Kaiser, Florian Reichenberger, Karla Köpke, Stefan-Martin Herrmann, Jacqueline Pfeifer, Hans-Dieter Orzechowski, Walter Zidek, Martin Paul and Eva Brand

in Human Molecular Genetics

Volume 12, issue 4, pages 423-433
Published in print February 2003 | ISSN: 0964-6906
Published online February 2003 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg040
Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation

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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.

Journal Article.  7397 words.  Illustrated.

Subjects: Genetics and Genomics

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