PCR-RFLP Detection of PAI-2 Variants in Myocardial Infarction

Abstract

PAI-2 is one of the regulators of the fibrinolytic system. The importance of the fibrinolytic cascades in the pathogenesis of myocardial infarction has been demonstrated by many investigators. Recently, some investigators have shown that two variants of PAI-2, designated A and B, are associated with the formation of large molecular PAI-2 complexes. This polymorphism is therefore present a genetic predisposition for the development of coronary artery disease and multiple sclerosis. Therefore, the prevalence of this polymorphism among 45 patients with MI and 20 control subjects was investigated. The AA genotype of the PAI-2 gene was found to be more frequent among those subjects with MI. These data provide evidence that a polymorphism of the PAI-2 gene is associated with an increased risk of MI.

Keywords

PAI-2 MI Polymorphism

References

1. Grant PJ , Prentice CLM . Coronary artery disease. In: Bloom AL , Forbes CD , Thomas DP , Tuddenhaw EGD , eds. Haemostasis and Thrombosis, vol. 2. Churchill Livingstone, Edinburgh and London, 1994:1231-1231.

2. Dan K , Andreasen PA , Grondhal-Hansen J , Kristensen P , Nielsen LS , Skriver L. Plasminogen activators, tissue degradation and cancer. Adv Cancer Res 1985;44:139-139.

3. Kruithof EKO , Vassali JK , Scleuning W-D , Mattaliano RJ , Bachmann P. Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937. JBiol Chem 1986;261:11207-11207.

4. Schleef RR , Wagner NV , Loskutoff DJ . Detection of both type 1 and type 2 plasminogen activator inhibitor. J Cell Physiol 1988;134:269-269.

5. Webb AC , Collins KL , Snyder SE , Alexander SJ , Rosenwasser LJ , Eddy RL , Shows TB , Auron PE. Human monocyte Arg-Serpin cDNA. Sequence, chromosomal assignment and homology to plasminogen activator-inhibitor. J Exp Med 1987;166:77-77.

6. Antolis TM , Clark MA , Barnes T , Lehrbach PR , Devine PL , Schevzov G , Goss NH , Stephens RW , Tolstoshev P . Cloning and expression of a cDNA coding for a human monocyte-derived plasminogen activator inhibitor. Proc Natl Acad Sci USA 1988;85:985-985.

7. Kise U , Kaudewitz H , Henschen A , Astedt B , Kruithof EKO , Bachnann F. Determination of intermediates, products and cleavage sites in the reaction between plasminogen activator inhibitor type 2 and urokinase. FEBS Lett 1988;230:51-51.

8. Ye RD , Wun TC , Sadler JE. cDNA cloning and expression in Eschericia coli of a plasminogen activator inhibitor from human placenta. J Biol Chem 1987;262:3718-3718.

9. Mikus P , Urano T , Lijestrom P , Ny T. Plasminogen-activator inhibitor type 2 (PAI-2) is a spontaneously polymerising SERPIN. Biochemical characterization of the recombinant intracellular and extracellular forms. Eur J Biochem 1993;218:1071-1071.

10.

10. Kruithof EKO , Gudinchet A , Bachmann F . Plasminogen activator inhibitor 1 and plasminogen activator inhibitor 2 in various disease states. Thromb Haemost 1988;59:7-7.

11.

11. Boekholdt SJ , Bijsterveld NR , Moons AHM , Levi M , Biller HR , Peters RJG. Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction. Circulation 2001;104:3063-3063.

12.

12. Eriksson P , Kallin B , Van't Hooft FM , 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;92:1851-1851.

13.

13. Ye S , Green FR , Scarabin PY , Nicaud V , et al. The 4G/5G genetic polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene associated with differences in plasma PAI-1 but not with risk of myocardial infarction in the ECTIM study. Thromb Haemost 1995;74:837-837.

14.

14. Foy CA , Grant PS . PCR-RFLP detection of PAI-2 gene variants: Prevalence in ethnic groups and disease relationship in patients undergoing coronary angiography. Thromb Haemost 1997;77(5):955-955.