Skip to main content
Top
Published in: Intensive Care Medicine 8/2007

01-08-2007 | Original

Increased mortality in septic shock with the 4G/4G genotype of plasminogen activator inhibitor 1 in patients of white descent

Authors: Gloria García-Segarra, Gerard Espinosa, Dolors Tassies, Josep Oriola, Jesús Aibar, Albert Bové, Pedro Castro, Joan-Carles Reverter, Josep-Maria Nicolás

Published in: Intensive Care Medicine | Issue 8/2007

Login to get access

Abstract

Objective

To evaluate the effect of the 4G/5G PAI-1 gene polymorphism on the development of organ failure and outcome in critically ill patients with septic syndromes.

Design and setting

Prospective, observational study in a medical intensive care unit of a university hospital.

Patients

224 consecutively admitted patients.

Interventions

Epidemiological data, severity scores, and the primary site of infection were recorded. DNA genotyping of the PAI-1, TNF-β, and IL1-ra genes, and measurement of plasma PAI-1 antigen and D-dimer were carried out.

Measurements

The primary outcome variables were organ dysfunction and mortality.

Results

Eighty-eight subjects had septic shock at ICU entry or within 48 h from admission. Homozygotes for the 4G allele exhibited higher plasma concentrations of PAI-1 antigen and D-dimer than 4G/5G and 5G/5G subjects). ICU mortality was 44.0% in patients with 4G/4G, 23.4% in 4G/5G and 12.5% in 5G/5G, mainly due to multiorgan failure. After adjusting for SAPS II at admission the genotypes independently associated with ICU mortality in septic shock were TNF-B2/B2 (OR 2.83, 1.04–7.67) and 4G/4G of PAI-1 (OR 2.23, 1.02–4.85). The PAI-1 genotype did not determine susceptibility to infection or the outcome in nonseptic systemic inflammatory response syndrome, sepsis, severe sepsis, and nosocomial septic shock.

Conclusions

Homozygosity for 4G of the PAI-1 gene confers an increase in the risk of mortality in adult patients with septic shock due to a greater organ failure.
Appendix
Available only for authorised users
Literature
1.
go back to reference Angus D, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310PubMedCrossRef Angus D, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310PubMedCrossRef
2.
go back to reference Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554PubMedCrossRef Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554PubMedCrossRef
3.
go back to reference Nadel S, Newport MJ, Boody Booy R, Levin M (1996) Variation in the tumor necrosis factor-alpha gene promoter region may be associated with death from meningococcal disease. J Infect Dis 174:878–880PubMed Nadel S, Newport MJ, Boody Booy R, Levin M (1996) Variation in the tumor necrosis factor-alpha gene promoter region may be associated with death from meningococcal disease. J Infect Dis 174:878–880PubMed
4.
go back to reference Waterer GW, Quasney MW, Cantor RM, Wunderink RG (2001) Septic shock and respiratory failure in community-acquired pneumonia have different TNF polymorphism associations. Am J Respir Crit Care Med 163:1599–1604PubMed Waterer GW, Quasney MW, Cantor RM, Wunderink RG (2001) Septic shock and respiratory failure in community-acquired pneumonia have different TNF polymorphism associations. Am J Respir Crit Care Med 163:1599–1604PubMed
5.
go back to reference Mira JP, Cariou A, Grall F, Delclaux C, Losser MR, Heshmati F, Cheval C, Monchi M, Teboul JL, Riche F, Leleu G, Arbibe L, Mignon A, Delpech M, Dhainaut JF (1999) Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. JAMA 282:561–568PubMedCrossRef Mira JP, Cariou A, Grall F, Delclaux C, Losser MR, Heshmati F, Cheval C, Monchi M, Teboul JL, Riche F, Leleu G, Arbibe L, Mignon A, Delpech M, Dhainaut JF (1999) Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study. JAMA 282:561–568PubMedCrossRef
6.
go back to reference Majetschak M, Flohe S, Obertacke U, Schroder J, Staubach K, Nast-Kolb D, Schade FU, Stuber F (1999) Relation of a TNF gene polymorphism to severe sepsis in trauma patients. Ann Surg 230:207–214PubMedCrossRef Majetschak M, Flohe S, Obertacke U, Schroder J, Staubach K, Nast-Kolb D, Schade FU, Stuber F (1999) Relation of a TNF gene polymorphism to severe sepsis in trauma patients. Ann Surg 230:207–214PubMedCrossRef
7.
go back to reference Fang XM, Schroder S, Hoeft A, Stuber F (1999) Comparison of two polymorphisms of the interleukin-1 gene family: interleukin-1 receptor antagonist polymorphism contributes to susceptibility to severe sepsis. Crit Care Med 27:1330–1334PubMedCrossRef Fang XM, Schroder S, Hoeft A, Stuber F (1999) Comparison of two polymorphisms of the interleukin-1 gene family: interleukin-1 receptor antagonist polymorphism contributes to susceptibility to severe sepsis. Crit Care Med 27:1330–1334PubMedCrossRef
8.
go back to reference Dellinger RP (2003) Inflammation and coagulation: implications for the septic patient. Clin Infect Dis 36:1259–1265PubMedCrossRef Dellinger RP (2003) Inflammation and coagulation: implications for the septic patient. Clin Infect Dis 36:1259–1265PubMedCrossRef
9.
go back to reference Kornelisse RF, Hazelzet JA, Savelkoul HFJ, Hop WC, Suur MH, Borsboom AN, Risseeuw-Appel IM, van der Voort E, de Groot R (1996) The relationship between plasminogen activator inhibitor-1 and proinflammatory and counter-inflammatory mediators in children with meningoccocal septic shock. J Infect Dis 173:1148–1156PubMed Kornelisse RF, Hazelzet JA, Savelkoul HFJ, Hop WC, Suur MH, Borsboom AN, Risseeuw-Appel IM, van der Voort E, de Groot R (1996) The relationship between plasminogen activator inhibitor-1 and proinflammatory and counter-inflammatory mediators in children with meningoccocal septic shock. J Infect Dis 173:1148–1156PubMed
10.
go back to reference Vervloet MG, Thijs LG, Hack CE (1998) Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. Semin Thromb Hemost 24:33–44PubMedCrossRef Vervloet MG, Thijs LG, Hack CE (1998) Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. Semin Thromb Hemost 24:33–44PubMedCrossRef
11.
go back to reference Mesters RM, Florke N, Ostermann H, Kienast J (1996) Increase of plasminogen activator inhibitor levels predicts outcome of leukopenic patients with sepsis. Thromb Haemost 75:902–907PubMed Mesters RM, Florke N, Ostermann H, Kienast J (1996) Increase of plasminogen activator inhibitor levels predicts outcome of leukopenic patients with sepsis. Thromb Haemost 75:902–907PubMed
12.
go back to reference Ryan MP, Kutz SM, Higgins PJ (1996) Complex regulation of plasminogen activator inhibitor type-1 (PAI-1) gene expression by serum and substrate adhesion. Biochem J 314:1041–1046PubMed Ryan MP, Kutz SM, Higgins PJ (1996) Complex regulation of plasminogen activator inhibitor type-1 (PAI-1) gene expression by serum and substrate adhesion. Biochem J 314:1041–1046PubMed
13.
go back to reference Horrevoets JG (2004) Plasminogen activator inhibitor 1 (PAI-1): in vitro activities and clinical relevance. Br J Haematol 125:12–23PubMedCrossRef Horrevoets JG (2004) Plasminogen activator inhibitor 1 (PAI-1): in vitro activities and clinical relevance. Br J Haematol 125:12–23PubMedCrossRef
14.
go back to reference Dawson SJ, Wiman B, Hamsten A, Green F, Humphries S, Henney AM (1993) The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 268:10739–10745PubMed Dawson SJ, Wiman B, Hamsten A, Green F, Humphries S, Henney AM (1993) The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 268:10739–10745PubMed
15.
go back to reference Hermans PW, Hibberd ML, Booy R, Daramola O, Hazelzet JA, de Groot R, Levin M (1999) 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Meningococcal Research Group. Lancet 354:556–560PubMedCrossRef Hermans PW, Hibberd ML, Booy R, Daramola O, Hazelzet JA, de Groot R, Levin M (1999) 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Meningococcal Research Group. Lancet 354:556–560PubMedCrossRef
16.
go back to reference Westendorp RG, Hottenga JJ, Slagboom PE (1999) Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock. Lancet 354:561–563PubMedCrossRef Westendorp RG, Hottenga JJ, Slagboom PE (1999) Variation in plasminogen-activator-inhibitor-1 gene and risk of meningococcal septic shock. Lancet 354:561–563PubMedCrossRef
17.
go back to reference Haralambous E, Hibberd ML, Hermans PW, Ninis N, Nadel S, Levin M (2003) Role of functional plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism in susceptibility, severity, and outcome of meningococcal disease in Caucasian children. Crit Care Med 31:2788–2793PubMedCrossRef Haralambous E, Hibberd ML, Hermans PW, Ninis N, Nadel S, Levin M (2003) Role of functional plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism in susceptibility, severity, and outcome of meningococcal disease in Caucasian children. Crit Care Med 31:2788–2793PubMedCrossRef
18.
go back to reference Menges T, Hermans PW, Little SG, Langefeld T, Boning O, Engel J, Sluijter M, de Groot R, Hempelmann G (2001) Plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism and prognosis of severely injured patients. Lancet 357:1096–1097PubMedCrossRef Menges T, Hermans PW, Little SG, Langefeld T, Boning O, Engel J, Sluijter M, de Groot R, Hempelmann G (2001) Plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism and prognosis of severely injured patients. Lancet 357:1096–1097PubMedCrossRef
19.
go back to reference Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R, Danesh J (2006) Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66:155 cases and 91:307 controls. Lancet 367:651–658PubMedCrossRef Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R, Danesh J (2006) Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66:155 cases and 91:307 controls. Lancet 367:651–658PubMedCrossRef
20.
go back to reference Sirgo G, Perez-Vela JL, Morales P, Del Rey M, Vendrell J, Gutierrez C, Rello J (2006) Association between 4G/5G polymorphism of the plasminogen activator inhibitor 1 gene with stroke or encephalopathy alter cardiac surgery. Intensive Care Med 32:668–675PubMedCrossRef Sirgo G, Perez-Vela JL, Morales P, Del Rey M, Vendrell J, Gutierrez C, Rello J (2006) Association between 4G/5G polymorphism of the plasminogen activator inhibitor 1 gene with stroke or encephalopathy alter cardiac surgery. Intensive Care Med 32:668–675PubMedCrossRef
21.
go back to reference Wiklund PG, Nilsson L, Ardnor SN, Eriksson P, Johansson L, Stegmayr B, Hamsten A, Holmberg D, Asplund K (2005) Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts. Stroke 36:1661–1665PubMedCrossRef Wiklund PG, Nilsson L, Ardnor SN, Eriksson P, Johansson L, Stegmayr B, Hamsten A, Holmberg D, Asplund K (2005) Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke: replicated findings in two nested case-control studies based on independent cohorts. Stroke 36:1661–1665PubMedCrossRef
22.
go back to reference Castello R, Espana F, Vazquez C, Fuster C, Almenar SM, Aznar J, Estelles A (2006) Plasminogen activator inhibitor-1 4G/5G polymorphism in breast cancer patients and its association with tissue PAI-1 levels and tumor severity. Thromb Res 117:487–492PubMedCrossRef Castello R, Espana F, Vazquez C, Fuster C, Almenar SM, Aznar J, Estelles A (2006) Plasminogen activator inhibitor-1 4G/5G polymorphism in breast cancer patients and its association with tissue PAI-1 levels and tumor severity. Thromb Res 117:487–492PubMedCrossRef
23.
go back to reference Hizawa N, Maeda Y, Konno S, Fukui Y, Takahashi D, Nishimura M (2006) Genetic polymorphisms at FCER1B and PAI-1 and asthma susceptibility. Clin Exp Allergy 36:872–876PubMedCrossRef Hizawa N, Maeda Y, Konno S, Fukui Y, Takahashi D, Nishimura M (2006) Genetic polymorphisms at FCER1B and PAI-1 and asthma susceptibility. Clin Exp Allergy 36:872–876PubMedCrossRef
24.
go back to reference Glueck CJ, Sieve L, Zhu B, Wang P (2006) Plasminogen activator inhibitor activity, 4G5G polymorphism of the plasminogen activator inhibitor 1 gene, and first-trimester miscarriage in women with polycystic ovary syndrome. Metabolism 55:345–352PubMedCrossRef Glueck CJ, Sieve L, Zhu B, Wang P (2006) Plasminogen activator inhibitor activity, 4G5G polymorphism of the plasminogen activator inhibitor 1 gene, and first-trimester miscarriage in women with polycystic ovary syndrome. Metabolism 55:345–352PubMedCrossRef
25.
go back to reference Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM (1988) CDC definitions for nosocomial infections. Am J Infect Control 16:128–140PubMedCrossRef Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM (1988) CDC definitions for nosocomial infections. Am J Infect Control 16:128–140PubMedCrossRef
26.
go back to reference Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, for the International Sepsis Definitions Conference (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250–1256PubMedCrossRef Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, for the International Sepsis Definitions Conference (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250–1256PubMedCrossRef
27.
go back to reference Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R (1994) The American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818–824PubMed Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R (1994) The American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818–824PubMed
28.
go back to reference Murray JF, Matthay MA, Luce JM, Flick MR (1988) An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 139:720–723 Murray JF, Matthay MA, Luce JM, Flick MR (1988) An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 139:720–723
29.
go back to reference Reber G, Bounameaux H, Perrier A, de Moerloose P (2001) Performances of a new, automated latex assay for the exclusion of venous thromboembolism. Blood Coagul Fibrinolysis 12:217–220PubMedCrossRef Reber G, Bounameaux H, Perrier A, de Moerloose P (2001) Performances of a new, automated latex assay for the exclusion of venous thromboembolism. Blood Coagul Fibrinolysis 12:217–220PubMedCrossRef
30.
go back to reference Declerck PJ (1988) Measurement of plasminogen activator inhibitor 1 in biological fluids with a murine monoclonal antibody-based enzyme-linked immuno-sorbant assay. Blood 71:220–225PubMed Declerck PJ (1988) Measurement of plasminogen activator inhibitor 1 in biological fluids with a murine monoclonal antibody-based enzyme-linked immuno-sorbant assay. Blood 71:220–225PubMed
31.
go back to reference Margaglione M, Grandone E, Cappucci G, Colaizzo D, Giuliani N, Vecchione G, d'Addedda M, Di Minno G (1997) An alternative method for PAI-1 promoter polymorphism (4G/5G) typing. Thromb Haemost 77:605–606PubMed Margaglione M, Grandone E, Cappucci G, Colaizzo D, Giuliani N, Vecchione G, d'Addedda M, Di Minno G (1997) An alternative method for PAI-1 promoter polymorphism (4G/5G) typing. Thromb Haemost 77:605–606PubMed
32.
go back to reference Schaaf BM, Seitzer U, Pravica V, Aries SP, Zabel P (2001) Tumor Necrosis Factor-a-308 promoter gene polymorphism and increased tumor necrosis factor serum bioactivity in farmer's lung patients. Am J Respir Crit Care Med 163:379–382PubMed Schaaf BM, Seitzer U, Pravica V, Aries SP, Zabel P (2001) Tumor Necrosis Factor-a-308 promoter gene polymorphism and increased tumor necrosis factor serum bioactivity in farmer's lung patients. Am J Respir Crit Care Med 163:379–382PubMed
33.
go back to reference Tarlow JK, Blakemore AIF, Lennard A, Solari R, Hughes HN, Steinkasserer A, Duff GW (1993) Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable number of an 86-bp tandem repeat. Hum Genet 91:403–404PubMedCrossRef Tarlow JK, Blakemore AIF, Lennard A, Solari R, Hughes HN, Steinkasserer A, Duff GW (1993) Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable number of an 86-bp tandem repeat. Hum Genet 91:403–404PubMedCrossRef
34.
go back to reference Stuber F, Petersen M, Bokelmann F, Schade U (1996) A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-alpha concentrations and outcome of patients with severe sepsis. Crit Care Med 24:381–384PubMedCrossRef Stuber F, Petersen M, Bokelmann F, Schade U (1996) A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-alpha concentrations and outcome of patients with severe sepsis. Crit Care Med 24:381–384PubMedCrossRef
35.
go back to reference Dempfle CE (2004) Coagulopathy in sepsis. Thromb Haemost 91:213–224PubMed Dempfle CE (2004) Coagulopathy in sepsis. Thromb Haemost 91:213–224PubMed
36.
37.
go back to reference Dhainaut JF, Shorr AF, Macias WL, Kollef MJ, Levi M, Reinhart K, Nelson DR (2005) Dynamic evolution of coagulopathy in the first day of severe sepsis: relationship with mortality and organ failure. Crit Care Med 33:341–348PubMedCrossRef Dhainaut JF, Shorr AF, Macias WL, Kollef MJ, Levi M, Reinhart K, Nelson DR (2005) Dynamic evolution of coagulopathy in the first day of severe sepsis: relationship with mortality and organ failure. Crit Care Med 33:341–348PubMedCrossRef
38.
go back to reference Mavrommatis AC, Theodoridis T, Economou M, Kotanidou A, El Ali M, Christopoulou-Kokkinou V, Zakynthinos SG (2001) Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock. Intensive Care Med 27:1853–1859PubMedCrossRef Mavrommatis AC, Theodoridis T, Economou M, Kotanidou A, El Ali M, Christopoulou-Kokkinou V, Zakynthinos SG (2001) Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock. Intensive Care Med 27:1853–1859PubMedCrossRef
39.
go back to reference Okabayashi K, Wada H, Ohta S, Shiku H, Nobori T, Maruyama K (2004) Hemostatic markers and the sepsis-related organ failure assessment score in patients with disseminated intravascular coagulation in an intensive care unit. Am J Hematol 76:225–229PubMedCrossRef Okabayashi K, Wada H, Ohta S, Shiku H, Nobori T, Maruyama K (2004) Hemostatic markers and the sepsis-related organ failure assessment score in patients with disseminated intravascular coagulation in an intensive care unit. Am J Hematol 76:225–229PubMedCrossRef
40.
go back to reference Hoekstra T, Geleijnse JM, Schouten EG, Kluft C (2002) Diurnal variation in PAI-1 activity predominantly confined to the 4G-allele of the PAI-1 gene. Thromb Haemost 88:794–798PubMed Hoekstra T, Geleijnse JM, Schouten EG, Kluft C (2002) Diurnal variation in PAI-1 activity predominantly confined to the 4G-allele of the PAI-1 gene. Thromb Haemost 88:794–798PubMed
41.
go back to reference Hattersley AT, McCarthy MI (2005) What makes a good genetic association study? Lancet 366:1315–1323PubMedCrossRef Hattersley AT, McCarthy MI (2005) What makes a good genetic association study? Lancet 366:1315–1323PubMedCrossRef
42.
go back to reference Boekholdt SM, Bjisterveld NR, Moons AH, Levi M, Buller HR, Peters RJ (2001) Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction: a systematic review. Circulation 104:3063–3068PubMed Boekholdt SM, Bjisterveld NR, Moons AH, Levi M, Buller HR, Peters RJ (2001) Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction: a systematic review. Circulation 104:3063–3068PubMed
43.
go back to reference Ding J, Nicklas BJ, Fallin MD, de Rekeneire N, Kritchevsky SB, Pahor M, Rodondi N, Li R, Zmuda JM, Harris TB (2006) Plasminogen activator inhibitor type 1 gene polymorphisms and haplotypes are associated with plasma plasminogen activator inhibitor type 1 levels but not with myocardial infarction or stroke. Am Heart J 152:1109–1115PubMedCrossRef Ding J, Nicklas BJ, Fallin MD, de Rekeneire N, Kritchevsky SB, Pahor M, Rodondi N, Li R, Zmuda JM, Harris TB (2006) Plasminogen activator inhibitor type 1 gene polymorphisms and haplotypes are associated with plasma plasminogen activator inhibitor type 1 levels but not with myocardial infarction or stroke. Am Heart J 152:1109–1115PubMedCrossRef
44.
go back to reference Goor ML van, Gomez Garcia E, Leebeek F, Brouwers GJ, Koudstaal P (2005) The plasminogen activator inhibitor (PAI-1) 4G/5G promoter polymorphism and PAI-1 levels in ischemic stroke. A case-control study. Thromb Haemost 93:92–96 Goor ML van, Gomez Garcia E, Leebeek F, Brouwers GJ, Koudstaal P (2005) The plasminogen activator inhibitor (PAI-1) 4G/5G promoter polymorphism and PAI-1 levels in ischemic stroke. A case-control study. Thromb Haemost 93:92–96
45.
go back to reference Lazo-Langner A, Knoll GA, Wells PS, Carson N, Rodger A (2006) The risk of dyalisis access thrombosis is related to the transforming growth factor-beta1 production haploptype and is modified by polymorphisms in the plasminogen activator inhibitor-type 1 gene. Blood 108:4052–4058PubMedCrossRef Lazo-Langner A, Knoll GA, Wells PS, Carson N, Rodger A (2006) The risk of dyalisis access thrombosis is related to the transforming growth factor-beta1 production haploptype and is modified by polymorphisms in the plasminogen activator inhibitor-type 1 gene. Blood 108:4052–4058PubMedCrossRef
46.
go back to reference Asselbergs FW, Williams SM, Hebert PR, Coffey CS, Hillege HL, Navis G, Vaughan DE, van Gilst WH, Moore JH (2006) The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin systems in determining plasma t-PA and PAI-1 levels. Thromb Haemost 96:471–477PubMed Asselbergs FW, Williams SM, Hebert PR, Coffey CS, Hillege HL, Navis G, Vaughan DE, van Gilst WH, Moore JH (2006) The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin systems in determining plasma t-PA and PAI-1 levels. Thromb Haemost 96:471–477PubMed
47.
go back to reference Festa A, Williams K, Tracy RP, Wagenknecht LE, Haffner SM (2006) Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident type-2 diabetes. Circulation 113:1753–1759PubMedCrossRef Festa A, Williams K, Tracy RP, Wagenknecht LE, Haffner SM (2006) Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident type-2 diabetes. Circulation 113:1753–1759PubMedCrossRef
48.
go back to reference Speleman L, Kerrebin JD, Look MP, Meeuwis CA, Foekens JA, Berns EM (2006) Prognostic value of plasminogen activator inhibitor-1 in head and neck squamous cell carcinoma. Head Neck 29:341–350CrossRef Speleman L, Kerrebin JD, Look MP, Meeuwis CA, Foekens JA, Berns EM (2006) Prognostic value of plasminogen activator inhibitor-1 in head and neck squamous cell carcinoma. Head Neck 29:341–350CrossRef
49.
go back to reference Offersen BV, Pfeiffer P, Andreassen P, Overgaard J (2007) Urokinase plasminogen activator and plasminogen activator inhibitor type-1 in nonsmall-cell lung cancer: relation to prognosis and angiogenesis. Lung Cancer 56:43–50PubMedCrossRef Offersen BV, Pfeiffer P, Andreassen P, Overgaard J (2007) Urokinase plasminogen activator and plasminogen activator inhibitor type-1 in nonsmall-cell lung cancer: relation to prognosis and angiogenesis. Lung Cancer 56:43–50PubMedCrossRef
50.
go back to reference Holmes CL, Russell JA, Walley KR (2003) Genetic polymorphisms in sepsis and septic shock: role in prognosis and potential for therapy. Chest 124:1103–1115PubMedCrossRef Holmes CL, Russell JA, Walley KR (2003) Genetic polymorphisms in sepsis and septic shock: role in prognosis and potential for therapy. Chest 124:1103–1115PubMedCrossRef
Metadata
Title
Increased mortality in septic shock with the 4G/4G genotype of plasminogen activator inhibitor 1 in patients of white descent
Authors
Gloria García-Segarra
Gerard Espinosa
Dolors Tassies
Josep Oriola
Jesús Aibar
Albert Bové
Pedro Castro
Joan-Carles Reverter
Josep-Maria Nicolás
Publication date
01-08-2007
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 8/2007
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-007-0695-y

Other articles of this Issue 8/2007

Intensive Care Medicine 8/2007 Go to the issue