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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2181.
Submitted July 19, 2002
Accepted October 2, 2002
The 4G5G polymorphism in the gene for PAI-1 and the circadian oscillation of plasma PAI-1
Johanna G van der Bom*, Michiel L Bots, Frits Haverkate, Cornelis Kluft, and Diederick E Grobbee
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands
Gaubius Laboratory, TNO-PG, Leiden, The Netherlands
Department of Epidemiology and Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands
* Corresponding author; email: j.g.vanderbom{at}jc.azu.nl.
Plasminogen activator inhibitor type I (PAI-1) antigen concentrations follows a circadian oscillation peaking in the morning. Some individuals show no apparent circadian rhythm, while others show up to a ten-fold variation in PAI-1 over 24 hours. Results from experimental studies suggest that a polymorphism in the promoter of the gene for PAI-1 (4G5G) directly influences the circadian expression of the PAI-1 gene. We studied whether the diurnal variation of PAI-1 antigen differs for the genotypes of the 4G5G polymorphism. A population-based cross-sectional study was performed among 263 subjects selected from the Rotterdam Study, a population-based cohort of 7983 men and women aged 55 years and over. The 4G allele was associated with a more pronounced circadian expression of PAI-1 antigen. Morning PAI-1 antigen concentrations were 79 ng/ml (95% confidence interval 68,92) in subjects homozygous for 4G, 62 ng/ml (54,72) in heterozygous subjects and 59 ng/ml (49,71) in subjects homozygous for 5G. While respective PAI-1 antigen concentrations in the afternoon were 40 ng/ml (33,49), 41 ng/ml (37,47) and 40 ng/ml (49,71). These findings suggest that the morning increase in PAI-1 antigen concentration is more pronounced among subjects homozygous for the 4G allele as compared to the morning increase among the other genotypes. Additionally, these findings show that homozygosity for the 4G allele is associated with increased PAI-1 levels only during the morning.
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