Artikel
Blood Pressure is Regulated by Differential Binding of Transcription Factor E2F-2 to the Endothelin-Converting Enzyme-1b Promoter
Differentielle Bindung des Transkriptionsfaktors E2F-2 am Endothelin-Converting Enzym-1b Promotor reguliert Blutdruck
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Veröffentlicht: | 11. November 2004 |
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Gliederung
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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 to 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 to -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.