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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2181.
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Blood, 1 March 2003, Vol. 101, No. 5, pp. 1841-1844
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
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
From the Julius Center for Health Sciences and Primary
Care, University Medical Center Utrecht; Van Creveldkliniek, University
Medical Center Utrecht; Gaubius Laboratory, TNO-PG, Leiden; and the
Department of Epidemiology and Biostatistics, Erasmus University
Medical Center, Rotterdam, the Netherlands.
Plasminogen activator inhibitor type I (PAI-1) antigen
concentrations follow a circadian oscillation peaking in the morning. Some individuals show no apparent circadian rhythm, while others show
up to a 10-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 older. 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 [CI],
68-92) in subjects homozygous for 4G, 62 ng/mL (95% CI, 54-72) in heterozygous subjects, and 59 ng/mL (95% CI,
49-71) in subjects homozygous for 5G. While respective PAI-1 antigen concentrations in the afternoon were 40 ng/mL (95% CI,
33-49), 41 ng/mL (95% CI, 37-47), and 40 ng/mL (95% CI, 49-71). These
findings suggest that the morning increase in PAI-1 antigen concentration is more pronounced among subjects homozygous for the
4G allele compared with the morning increase among the
other genotypes. Additionally, these findings show that homozygosity for the 4G allele is associated with increased PAI-1 levels
during the morning only.
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