4G/5G PAI-1 Promoter Polymorphism and Acute-Phase Levels of PAI-1 Following Coronary Bypass Surgery: A Prospective Study

Burzotta, Francesco; Iacoviello, Licia; Castelnuovo, Augusto Di; Zamparelli, Roberto; D’Orazio, Andria; Amore, C.; Schiavello, R; Donati, Maria Benedetta; Maseri, Attilio; Possati, Gianfederico; Andreotti, Felicita

doi:10.1023/b:thro.0000024052.79415.62

Cited by 23 publications

(20 citation statements)

References 26 publications

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“…However, the association between carriage of the PAI-1 5G allele and change in PAI-1 mRNA, with greater reduction in PAI-1 mRNA in carriers of the 5G allele, may be an equivalent finding. This is in concordance with previous studies demonstrating lower PAI-1 levels in patients homozygous for 5G (24,1).…”

Section: Discussionsupporting

confidence: 83%

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Coagulopathy After Cardiac Surgery May Be Influenced by a Functional Plasminogen Activator Inhibitor Polymorphism

Duggan

O'Dwyer²,

Caraher³

et al. 2007

Anesthesia &Amp; Analgesia

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BACKGROUND: Cytokine-mediated inflammation and coagulopathy may occur after cardiac surgery. In this study we investigated the temporal pattern of plasminogen activator inhibitor-1 (PAI-1) gene expression after cardiac surgery and its relation with PAI genotype, and obtained preliminary data regarding its relation to perioperative morbidity. METHODS: The relative change in PAI-1 mRNA 1, 6, and 24 h after cardiopulmonary bypass (CPB) was measured from mononuclear cells in 82 patients undergoing elective cardiac surgery. DNA was analyzed for carriage of the 4G/5G PAI-1 polymorphism. RESULTS: PAI-1 gene expression decreased after CPB in all patients. A larger reduction in PAI-1 gene expression was observed in homozygous carriers of the 5G allele. Homozygous carriers of the 5G allele were also more likely to receive transfusion of coagulation blood products. There was no relation between change in PAI-1 gene expression and duration of CPB. CONCLUSIONS: PAI-1 gene expression decreased over time after CPB. We found a link between PAI-1 genotype, PAI gene expression, and transfusion of coagulation products after cardiac surgery.

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Section: Discussionsupporting

confidence: 83%

“…Patients carrying the 4G allele have a 20% higher basal level of PAI-1 than those carrying the 5G allele (24). Our methods of measuring change in mRNA without an absolute measurement of mRNA concentrations does not permit a comparison of absolute PAI-1 mRNA levels with previously published PAI-1 protein concentrations.…”

Section: Discussionmentioning

confidence: 78%

Coagulopathy After Cardiac Surgery May Be Influenced by a Functional Plasminogen Activator Inhibitor Polymorphism

Duggan

O'Dwyer²,

Caraher³

et al. 2007

Anesthesia &Amp; Analgesia

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“…Since the PAI-1 4G variant has been shown to be associated with higher PAI-1 levels in plasm [12][13][14] and in tissue, [15][16][17] our data suggest that PAI-1 promotes neointima proliferation. This hypothesis for the role of PAI-1 is supported by a number of reports on a positive correlation between post-PTCA PAI-1 levels or activity and restenosis, 18-23 but contradicted by one study which could not find an association between the PAI-1 4G/5G polymorphism and restenosis.…”

Section: Discussionmentioning

confidence: 70%

“…The functionality of PAI-1 has been extensively investigated and the majority of results indicate that the 4G variant leads to higher expression levels. 12,13,[15][16][17] In contrast, little evidence is avail-able regarding APC levels in Factor V Leiden carriers and carriers of the PAI-1 4G/5G genotypes. P. Weiler et al observed only marginal augmentation of protein C activation in Factor V Leiden-mice.…”

Section: Limitations Of the Studymentioning

confidence: 99%

The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions

Pons¹,

Monraats²,

Maat³

et al. 2007

Thromb Haemost

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Since activation of the hemostatic system is an important feature of the wound healing response triggered by arterial injury, variations in genes involved in thrombus formation may play a role in restenosis after percutaneous coronary interventions (PCI). Therefore, our aim was to examine the relationship between polymorphisms that are known to play a role in the hemostatic system and the risk of clinical restenosis in the GENetic DEterminants of Restenosis (GENDER) study, a multicenter prospective study design that enrolled 3,104 consecutive patients after successful PCI. Target Vessel Revascularization (TVR) was the primary endpoint. All patients were genotyped for 6 polymorphisms in the Factor II, Factor V, Factor VII and PAI-1 genes.The PAI-1 4G variant was associated with an increased risk of TVR. When compared to 5G/5G homozygotes, heterozygous patients were at higher risk for TVR (HR: 1.46, 95%CI: 1.05-2.03), whereas patients with the 4G/4G genotype had an even further increased risk (HR: 1.69, 95%CI: 1.19-2.41). In contrast, the factor V 506Gln (Factor V Leiden) amino acid substitution was associated with a decreased risk of TVR (HR: 0.41, 95%CI: 0.19-0.86).Our findings indicate that polymorphisms in the Factor V and PAI-1 genes may play a role in the process of restenosis.43

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“…For example, PAI-1 levels in the blood are increased within 1 h of major surgery, severe trauma, and myocardial infarction (D'Angelo, Kluft et al 1985;Kluft, Verheijen et al 1985;Burzotta, Iacoviello et al 2003;. A major source of PAI-1 is liver because it is an acute phase protein ).…”

Section: Introductionmentioning

confidence: 99%

Plasminogen activator inhibitor 1: Mechanisms of its synergistic regulation by growth factors

Song

2010

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4G/5G PAI-1 Promoter Polymorphism and Acute-Phase Levels of PAI-1 Following Coronary Bypass Surgery: A Prospective Study

Abstract: 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.

Cited by 23 publications

References 26 publications

Coagulopathy After Cardiac Surgery May Be Influenced by a Functional Plasminogen Activator Inhibitor Polymorphism

Coagulopathy After Cardiac Surgery May Be Influenced by a Functional Plasminogen Activator Inhibitor Polymorphism

The influence of established genetic variation in the haemostatic system on clinical restenosis after percutaneous coronary interventions

Plasminogen activator inhibitor 1: Mechanisms of its synergistic regulation by growth factors

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