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  • Title: Circadian clock genes cause activation of the human PAI-1 gene promoter with 4G/5G allelic preference.
    Author: Chong NW, Codd V, Chan D, Samani NJ.
    Journal: FEBS Lett; 2006 Aug 07; 580(18):4469-72. PubMed ID: 16857194.
    Abstract:
    Increased plasminogen activator inhibitor-1 (PAI-1) activity is associated with greater risk of myocardial infarction. PAI-1 expression is regulated by a 4G/5G promoter polymorphism. The 4G allele is associated with higher PAI-levels and greater circadian variation. Here we show that clock protein heterodimers BMAL/CLOCK cause greater activation (approximately 2-fold, P<0.05) of the 4G allele. Site-directed mutagenesis studies suggest that clock genes act on two canonical E-boxes to regulate PAI-1 promoter activity. These results identify a potential novel mechanism whereby allele-specific clock genes - mediated modulation of PAI-1 expression may contribute to circadian variation in cardiac risk.
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