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 (≈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. © 2006 Federation of European Biochemical Societies.
Chong, N. W., Codd, V., Chan, D., & Samani, N. J. (2006). Circadian clock genes cause activation of the human PAI-1 gene promoter with 4G/5G allelic preference. FEBS Letters, 580(18), 4469–4472. https://doi.org/10.1016/j.febslet.2006.07.014