Document Type : Original Article

Authors

1 Researcher and lecture assistant at the Medical Laboratory Science Department, Knowledge University, Kurdistan Region, Erbil, Iraq

2 Human Genetics Division, Medical Biotechnology Department, National Institute of Genetics Engineering and Biotechnology, Tehran, Iran

3 Personalized Medicine Research Center of AmitisGen, Tehran, Iran

Abstract

PAI-1 has become recognized as a central molecule linking pathogenesis and progression of thrombotic vascular events, including stroke. Clinical and experimental studies show that PAI-1 deficiencies cause accelerated fibrinolysis and bleeding, whereas elevated PAI-1 plasma levels are associated with vascular thrombosis. Raised PAI1 plasma levels are related to a 1-bp guanine deletion/insertion (4G/5G) polymorphism in the promoter of the PAI1 gene. The 4G allele is associated with higher plasma PAI1 transcription and activity. In the current study, the association of higher PAI-1 plasma levels and the prevalence of the 4G/5G polymorphism in the PAI-1 gene promoter region in young patients with stroke were explored. Significantly, higher PAI-1 levels were observed in patients when compared to controls (p =002). The 4G/5G polymorphisms were significantly associated with increased PAI-1 levels, with the variant homozygous 4G/4G corresponding to mean values in patients versus controls.

Keywords

  1. Dawson SJ, Wiman B, Hamsten A, et al. 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. JBiolChem. 1993;268(15):10739-10745.
  2. Klinger KW, Winqvist R, Riccio A, et al. Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis. Proc Natl Acad Sci U S A. 1987;84(23):8548-8552.
  3. Klinger KW, Winqvist R, Riccio A, et al. Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis. Proc Natl Acad Sci U S A. 1987;84(23):8548-8552.
  4. Tsai SJ, Hong CJ, Liou YJ, Yu YW, Chen TJ. Plasminogen activato inhibitor-1 gene is associated with major depression and antidepressant treatment response. Pharmacogenet Genomics 2008;18(10):869-875.

 

  1. Hoekstra T, Geleijnse JM, Kluft C, Giltay EJ, Kok FJ, Schouten EG. 4G/4G genotype of PAI-1 gene is associated with reduced risk of stroke in elderly Stroke. 2003;34:2822–2829.
  2. Catto AJ, Carter AM, Stickland M, et al. Plasminogen activator inhibitor-1(PAI-1) 4G/5G promoter polymorphism and levels in subjects with cerebrovascular disease. Thromb Haemost. 1997;77:730 –734.
  3. Heijmans BT, Westendorp RG, Knook DL, et al. Angiotensin I-converting enzyme and plasminogen activator inhibitor-1 gene variants: risk of mortality and fatal cardiovascular disease in an elderly population-based cohort. J Am Coll Cardiol. 1999;34:1176 –1183.
  4. Roest M, van der Schouw YT, Banga JD, et al. Plasminogen activator inhibitor 4G polymorphism is associated with decreased risk of cerebrovascular mortality in older women. Circulation. 2000;101:67–70.
  5. Elbaz A, Cambien F, Amarenco P. Plasminogen activator inhibitor genotype and brain infarction. Circulation. 2001;103:E13–E14. Endler G, Lalouschek W, Exner M, et al. The 4G/4G genotype at nucleotide position -675 in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene is less frequent in young patients with minor stroke than in controls. Br J Haematol. 2000;110:469 – 471.
  6. Hindorff LA, Schwartz SM, Siscovick DS, et al. The association of PAI-1 promoter 4G/5G insertion/deletion polymorphism with myocardial infarction and stroke in young women. J Cardiovasc Risk. 2002;9:131–137.
  7. Petrovic D, Milanez T, Kobal J, et al. Prothrombotic gene polymorphisms and atherothrombotic cerebral infarction. Acta Neurol Scand. 2003;108:109 –113.
  8. Eriksson P, Kallin B, ’t Hooft FM, et al. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci U S A. 1995;92: 1851–1855.

 

  1. Hoekstra T, Geleijnse JM, Kluft C, Giltay EJ, Kok FJ, Schouten EG. 4G/4G genotype of PAI-1 gene is associated with reduced risk of stroke in elderly Stroke. 2003;34:2822–2829.
  2. Catto AJ, Carter AM, Stickland M, et al. Plasminogen activator inhibitor-1(PAI-1) 4G/5G promoter polymorphism and levels in subjects with cerebrovascular disease. Thromb Haemost. 1997;77:730 –734.

15.Heijmans BT, Westendorp RG, Knook DL, et al. Angiotensin I-converting enzyme and plasminogen activator inhibitor-1 gene variants: risk of mortality and fatal cardiovascular disease in an elderly population-based cohort. J Am Coll Cardiol. 1999;34:1176 –1183.

  1. Roest M, van der Schouw YT, Banga JD, et al. Plasminogen activator inhibitor 4G polymorphism is associated with decreased risk of cerebrovascular mortality in older women. Circulation. 2000;101:67–70.
  2. Elbaz A, Cambien F, Amarenco P. Plasminogen activator inhibitor genotype and brain infarction. Circulation. 2001;103:E13–E14.
  3. Endler G, Lalouschek W, Exner M, et al. The 4G/4G genotype at nucleotide position -675 in the promotor region of the plasminogen activator inhibitor 1 (PAI-1) gene is less frequent in young patients with minorstroke than in controls. Br J Haematol. 2000;110:469 – 471.
  4. Hindorff LA, Schwartz SM, Siscovick DS, et al. The association of PAI-1 promoter 4G/5G insertion/deletion polymorphism with myocardial infarction and stroke in young women. J Cardiovasc Risk. 2002;9:131–137.
  5. Petrovic D, Milanez T, Kobal J, et al. Prothrombotic gene polymorphisms and atherothrombotic cerebral infarction. Acta Neurol Scand. 2003;108:109 –113.