4G/5G PAI-1 promoter polymorphism and acute-phase levels of PAI-1 following coronary bypass surgery: A prospective study

Francesco Burzotta, Licia Iacoviello, Augusto Di Castelnuovo, Roberto Zamparelli, Andria D'Orazio, Concetta Amore, Rocco Schiavello, Maria Benedetta Donati, Attilio Maseri, GianFederico Possati, Felicita Andreotti

Research output: Contribution to journalArticle

Abstract

Background and objective: The 4G/5G plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism has been associated with basal PAI-1 levels, with ischemic heart disease, and with adverse prognosis in critically ill patients. We hypothesized it might also influence the acute-phase levels of PAI-1 following coronary bypass surgery. Methods: In 111 consecutive patients undergoing elective coronary bypass surgery, 4G/5G genotyping and serial plasma PAI-1 activity and antigen levels were prospectively measured before surgery, daily up to 72 h, and at discharge. The inflammatory reaction was additionally assessed by white cell count, fibrinogen, interleukin-6, and C-reactive protein levels. Results: PAI-1 activity and antigen concentrations increased approximately two-fold after surgery, peaking at 48 hours. Carriers of the 4G-allele, compared with 5G/5G homozygotes, showed approximately 20% higher PAI-1 activity and antigen both preoperatively (P = 0.007 and P = 0.035) and after surgery. White cell count, fibrinogen, interleukin-6, and C-reactive protein values did not differ significantly according to genotypic groups. In multivariate analysis, the 4G/5G genotype was the only significant modulator of postoperative PAI-1 activity (P = 0.003) and the main significant modulator of postoperative PAI-1 antigen (P = 0.013). No significant interaction was found between the effects of time and genotype on postoperative PAI-1. This indicates that the association between 4G/5G and acute-phase PAI-1 levels is secondary to the genotype-related difference of baseline PAI-1. Conclusions: Postoperative PAI-1 concentrations of patients undergoing elective coronary bypass surgery are higher in carriers of the 4G-allele than in 5G/5G homozygotes as a result of higher baseline values. Knowledge of 4G/5G status may be useful to predict acute-phase PAI-1 concentrations.

Original languageEnglish
Pages (from-to)149-154
Number of pages6
JournalJournal of Thrombosis and Thrombolysis
Volume16
Issue number3
DOIs
Publication statusPublished - Dec 2003

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Keywords

  • Acute-phase response
  • Coronary bypass
  • Gene polymorphism
  • PAI-1

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Burzotta, F., Iacoviello, L., Di Castelnuovo, A., Zamparelli, R., D'Orazio, A., Amore, C., Schiavello, R., Donati, M. B., Maseri, A., Possati, G., & Andreotti, F. (2003). 4G/5G PAI-1 promoter polymorphism and acute-phase levels of PAI-1 following coronary bypass surgery: A prospective study. Journal of Thrombosis and Thrombolysis, 16(3), 149-154. https://doi.org/10.1023/B:THRO.0000024052.79415.62