RSS-Feed abonnieren
DOI: 10.1055/s-0038-1649875
Plasminogen Activator Inhibitor-1 (PAI-1) Promoter Polymorphism and Coronary Artery Disease in Non-Insulin-Dependent Diabetes
Publikationsverlauf
Received 30. März 1995
Accepted after resubmission 05. Juli 1995
Publikationsdatum:
09. Juli 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199504/lookinside/thumbnails/10-1055-s-0038-1649875-1.jpg)
Summary
Elevated levels of PAI-1 are found in coronary artery disease (CAD) and non-insulin-dependent diabetes (NIDDM). PAI-1 may be involved in the pathogenesis of CAD through suppression of fibrinolysis, alternatively the high levels may result from vascular damage. There is evidence that PAI-1 levels are related to genotype at a PAI-1 promoter polymorphism. Genotype at this 4G/5G polymorphism was determined in 160 NIDDM (90 males and 70 females) patients with (n = 38) or without (n = 122) clinical evidence of CAD. Levels of cholesterol were higher (6.5 vs 5.9 mM, p <0.01) and of PAI-1 tended to be higher (PAI-1 activity 23.0 vs 20.4 U/ml) with CAD. The frequency of the 4G/4G genotype was increased and the 5G/5G genotype decreased, in the group CAD compared to those without (p <0.05). These results suggest that possession of the 4G/4G PAI-1 promoter genotype is a risk factor for the development of CAD in subjects with NIDDM.
-
References
- 1 ECAT Angina Pectoris Study Group. ECAT angina pectoris study: baseline associations of haemostatic factors with extent of coronary arteriosclerosis and other coronary risk factors in 3000 patients with angina pectoris undergoing coronary angiography. Eur Heart J 1993; 14: 8-17
- 2 Hamsten A, de Faire U, Walldius G, Dahlén G, Szamosi A, Landou C, Blombäck M, Wiman B. Plasminogen activator inhibitor in plasma: Risk for recurrent myocardial infarction. Lancet 1987; 2: 3-9
- 3 Potter van Loon BJ, Kluft K, Radder JK, Blankenstein MA, Meinders AE. The cardiovascular risk factor plasminogen activator inhibitor type 1 is related to insulin resistance. Metabolism 1993; 42: 945-949
- 4 Landin K, Tengborn L, Smith U. Elevated fibrinogen and plasminogen activator inhibitor (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease. J Int Med 1990; 227: 273-278
- 5 Landin K, Stigendal L, Eriksson E, Krotkiewski M, Risberg B, Tengborn L, Smith U. Abdominal obesity is associated with an impaired fibrinolytic activity and elevated plasminogen activator inhibitor-!. Metabolism 1990; 39: 1044-1048
- 6 Juhan-Vague I, Roul C, Alessi MC, Ardissone JP, Heim M, Vague P. Increased plasminogen activator inhibitor activity in non insulin dependent diabetic patients - relationship with plasma insulin. Thromb Haemost 1989; 61: 370-373
- 7 Juhan-Vague I, Alessi MC, Joly P, Thirion W, Vague P, Declerck PJ, Serradimigni A, Collen D. Plasma plasminogen activator inhibitor-1 in angina pectoris. Influence of plasma insulin and acute phase-response Arteriosclerosis 1989; 9: 362-367
- 8 Juhan-Vague I, Vague P, Alessi MC, Badier C, Valadier J, Aillaud MF, Atlan C. Relationships between plasma insulin, triglyceride, body mass index and plasminogen activator inhibitor 1. Diabetes Metab 1987; 13: 331-336
- 9 Mehta J, Mehta P, Lawson D, Saldeen T. Plasma tissue plasminogen activator inhibitor levels in coronary artery disease: Correlations with age and triglyceride concentrations. J Am Coll Cardiol 1987; 9: 263-268
- 10 Dawson S, Wiman B, Hamsten A, Green F, Humphries S, Henney A. 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 1993; 268: 10739-10745
- 11 Panahloo A, Mohamed-Ali V, Lane A, Green F, Humphries S, Yudkin J. Determinants of plasminogen activator inhibitor 1 activity in treated NIDDM and its relation to a polymorphism in the plasminogen activator inhibitor 1 gene. Diabetes 1995; 44: 37-42
- 12 Gough SC L, Grant PJ. The fibrinolytic system in diabetes mellitus. Diabetic Med 1991; 8: 898-905
- 13 Mansfield MW, Stickland MH, Carter AM, Grant PJ. Polymorphisms of the plasminogen activator inhibitor-1 gene in type 1 and type 2 diabetes and in patients with diabetic retinopathy. Thromb Haemost 1994; 71: 731-736
- 14 Mansfield MW, Stickland MH, Grant PJ. Environmental and genetic factors in relation to elevated circulating levels of plasminogen activator inhibitor-1 in Caucasian patients with non-insulin-dependent diabetes mellitus. Thromb Haemost. 1995 (In press)
- 15 Schneiderman J, Sawdey MS, Keeton MR, Bordin GM, Bernstein EF, Dilley RB, Loskutoff DJ. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. Proc Natl Acad Sci USA 1992; 89: 6998-7002
- 16 Dawson S, Hamsten A, Wiman B, Henney A, Humphries S. Genetic variation at the plasminogen activator inhibitor-1 locus is associated with altered levels of plasma plasminogen activator inhibitor-1 activity. Arterioscler Thromb 1991; 11: 183-190
- 17 Eriksson P, Kallin B, van’t Hooft F, Bavenholm P, Hamsten A. Allele- specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci USA 1995; 92: 1851-1855