4G/5G PAI-1 promoter polymorphism and acute-phase levels of PAI-1 following coronary bypass surgery: a prospective study.
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.
Burzotta
Francesco
F
Department of Cardiovascular Medicine, Catholic University, Rome, Italy.
Iacoviello
Licia
L
Di Castelnuovo
Augusto
A
Zamparelli
Roberto
R
D'Orazio
Andria
A
Amore
Concetta
C
Schiavello
Rocco
R
Donati
Maria Benedetta
MB
Maseri
Attilio
A
Possati
GianFederico
G
Andreotti
Felicita
F
D000210:Acute-Phase Reaction / Q000097:blood* / Q000209:etiology / Q000235:genetics; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D013997:Time Factors
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1