Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation
Differential binding of transcription factor E2F-2 to the endothelin-converting enzyme-1b promoter affects blood pressure regulation
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DOI：
10.1093/hmg/ddg040
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发表时间：
2003-02-15
影响因子：
3.5
通讯作者：
Brand, E
中科院分区：
文献类型：
--
作者：
Funke-Kaiser, H;Reichenberger, F;Brand, E
内皮素转换酶（ECE）-1基因是调节血压的候选基因，我们报道了新的基因变异体T-839 G、C-338 A、L75 F、A677 V和C+295 T的鉴定。与野生型启动子相比，瞬时转染含有-338A等位基因的报告构建体显示启动子活性增加。EMSA显示E2 F-2与ECE-1b启动子序列的特异性结合，与-338C相比，-338A等位基因与E2 F-2的亲和力增加相关。在704例高血压患者中分析了这一发现的临床相关性。在未经治疗的高血压女性中，-338A和-839G等位基因与动态血压值显著相关。这项研究提供了细胞周期相关的E2 F家族和血压调节之间的联系，通过内皮素系统的一个组成部分的第一个证据。
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.