Please use this identifier to cite or link to this item:
|Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL|
A single-nucleotide polymorphism in the human p27kip1 gene (-838C>A) affects basal promoter activity and the risk of myocardial infarction
|Authors:||González, Pelayo; Díez-Juan, Antonio; Coto, Eliecer; Victoria, Álvarez; Reguero, Julian R.; Batalla, Alberto; Andrés, Vicente|
|Citation:||BMC Biology 2004, 2:5|
|Abstract:||[Background] Excessive proliferation of vascular smooth muscle cells and leukocytes within the artery wall is a major event in the development of atherosclerosis. The growth suppressor p27kip1 associates with several cyclin-dependent kinase/cyclin complexes, thereby abrogating their capacity to induce progression through the cell cycle. Recent studies have implicated p27kip1 in the control of neointimal hyperplasia. For instance, p27kip1 ablation in apolipoprotein-E-null mice enhanced arterial cell proliferation and accelerated atherogenesis induced by dietary cholesterol. Therefore, p27kip1 is a candidate gene to modify the risk of developing atherosclerosis and associated ischaemic events (i.e., myocardial infarction and stroke).|
[Results] In this study we found three common single-nucleotide polymorphisms in the human p27kip1 gene (+326T>G [V109G], -79C>T, and -838C>A). The frequency of -838A carriers was significantly increased in myocardial infarction patients compared to healthy controls (odds ratio [OR] = 1.73, 95% confidence interval [95%CI] = 1.12–2.70). In addition, luciferase reporter constructs driven by the human p27kip1 gene promoter containing A at position -838 had decreased basal transcriptional activity when transiently transfected in Jurkat cells, compared with constructs bearing C in -838 (P = 0.04).
[Conclusions] These data suggest that -838A is associated with reduced p27kip1 promoter activity and increased risk of myocardial infarction.
|Description:||This article is available from: http://www.biomedcentral.com/1741-7007/2/5|
|Appears in Collections:||(IBV) Artículos|