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, Gian Federico Possati, Felicita Andreotti

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)149-154
Numero di pagine6
RivistaJournal of Thrombosis and Thrombolysis
Volume16
Stato di pubblicazionePubblicato - 2003

Keywords

  • PAI-1
  • Reazione di fase acuta
  • Bypass coronarico
  • Polimorfismo genico

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