The 4G5G polymorphism in the gene for PAI-1 and the circadian oscillation of plasma PAI-1.
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.
van der Bom
Johanna G
JG
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht; Van Creveldkliniek, The Netherlands. j.g.vanderbom@jc.azu.nl
Bots
Michiel L
ML
Haverkate
Frits
F
Kluft
Cornelis
C
Grobbee
Diederick E
DE
D056930:ARNTL Transcription Factors; D000368:Aged; D000483:Alleles; D051792:Basic Helix-Loop-Helix Proteins; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002940:Circadian Rhythm / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D009426:Netherlands; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014157:Transcription Factors / Q000502:physiology
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D017395:Plasminogen Activator Inhibitor 1; D014157:Transcription Factors; C486615:BMAL2 protein, human