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

15 Citations (Scopus)

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

Fingerprint

Plasminogen Activator Inhibitor 1
Prospective Studies
Antigens
Genotype
Homozygote
C-Reactive Protein
Fibrinogen
Interleukin-6
Cell Count
Alleles
Critical Illness
Myocardial Ischemia
Multivariate Analysis

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

4G/5G PAI-1 promoter polymorphism and acute-phase levels of PAI-1 following coronary bypass surgery : A prospective study. / Burzotta, Francesco; Iacoviello, Licia; Di Castelnuovo, Augusto; Zamparelli, Roberto; D'Orazio, Andria; Amore, Concetta; Schiavello, Rocco; Donati, Maria Benedetta; Maseri, Attilio; Possati, GianFederico; Andreotti, Felicita.

In: Journal of Thrombosis and Thrombolysis, Vol. 16, No. 3, 12.2003, p. 149-154.

Research output: Contribution to journalArticle

Burzotta, Francesco ; Iacoviello, Licia ; Di Castelnuovo, Augusto ; Zamparelli, Roberto ; D'Orazio, Andria ; Amore, Concetta ; Schiavello, Rocco ; Donati, Maria Benedetta ; Maseri, Attilio ; Possati, GianFederico ; Andreotti, Felicita. / 4G/5G PAI-1 promoter polymorphism and acute-phase levels of PAI-1 following coronary bypass surgery : A prospective study. In: Journal of Thrombosis and Thrombolysis. 2003 ; Vol. 16, No. 3. pp. 149-154.
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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.",
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T1 - 4G/5G PAI-1 promoter polymorphism and acute-phase levels of PAI-1 following coronary bypass surgery

T2 - A prospective study

AU - Burzotta, Francesco

AU - Iacoviello, Licia

AU - Di Castelnuovo, Augusto

AU - Zamparelli, Roberto

AU - D'Orazio, Andria

AU - Amore, Concetta

AU - Schiavello, Rocco

AU - Donati, Maria Benedetta

AU - Maseri, Attilio

AU - Possati, GianFederico

AU - Andreotti, Felicita

PY - 2003/12

Y1 - 2003/12

N2 - 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.

AB - 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.

KW - Acute-phase response

KW - Coronary bypass

KW - Gene polymorphism

KW - PAI-1

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