The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk

Tsantes, Argirios Ε.; Nikolopoulos, Georgios K.; Bagos, Pantelis G.; Bonovas, Stefanos; Kopterides, Petros; Vaiopoulos, G

doi:10.1016/j.thromres.2007.09.005

Cited by 93 publications

(75 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…9 PAI-1 4G-4G has come out as the leader factor in the SVT group, and in the various subgroups, confirming its important role in pathogenesis of SVT, as Balta et al 10 have found, and confirming itself as a thrombotic risk factor in different target organs, as showed by Tsantes et al 11 MTHFR 677TT genotype was strongly associated with portal thrombosis in our cirrhotic patients as reported previously by Amitrano et al 12 Hardy-Weinberg equilibrium for PAI-1 and MTHFR 677 was deviated from that expected from a population (PAI-1 x 2 41.96, P < 0.0001; MTHFR 677 x 2 15.00, P 0.0001). We think that PAI-1 4G-4G and MTHFR 677TT can increase the inflammation response, participating to the activation of perisinusoidal hepatic stellate cells, causing hepatic fibrosis and augmented intrahepatic vascular resistance typical of the LC, as suggested by Fernandez.…”

Section: Discussionmentioning

confidence: 62%

PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and Prothrombin 20210A in Splanchnic Vein Thrombosis: Analysis of Individual Patient Data From Three Prospective Studies

Pasta¹,

Pasta

D’Amico

2016

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

Background: There are no univocal opinions on the role of genetic thrombophilia on splanchnic vein thrombosis (SVT). We defined genetic thrombophilia the presence of one of these thrombophilic genetic factors (THRGFs): PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and prothrombin 20210A. Objectives: To evaluate the frequencies of these THRGFs in SVT patients, we analyzed individual data of 482 Caucasian patients, recruited from 2000 to 2014 in three prospective studies. SVT was defined as the presence of thrombosis of portal (PVT), mesenteric (MVT), splenic (SPVT), cava (CT), and hepatic vein (Budd Chiari syndrome, BCS). Pre-hepatic SVT (pre-HSVT) was defined as PVT with or without MVT/SPVT, without BCS. Post-hepatic SVT (post-HSVT) was BCS with or without PVT/MVT/SPVT. Methods: We compared 350 patients with liver cirrhosis (LC), 47 hepatocellular carcinoma (HCC), 37 myeloproliferative neoplasm (MPN), 38 associated disease (AD), 10 without any associated disease (WAD), vs 150 healthy controls (HC); 437 patients showed pre-HSVT and 45 post-HSVT. Results: Thrombophilia was present in 294/482 (60.9%) patients: 189/350 LC (54.0%), 31/47 (66.0%) HCC, 29/39 (74.4%) MPN, 35/38 AD (92.1%), and 10/10 (100%) WAD, and 54/150 (36.0%) in HC. In the total group, we found 175 PAI-1 4G-4G, 130 MTHFR 677TT, 42V Leiden 506Q, and 27 prothrombin 20210A; 75 patients showed presence of >1 TRHGF; the more frequent association was PAI-1 4G-4G/MTHFR 677TT, in 36 patients. PAI-1 4G-4G and MTHFR 677TT were significantly more frequent in patients with SVT (P values <0.005), whereas V Leiden Q506 and prothrombin G20210A were not. PAI-1 4G-4G and MTHFR 677TT distributions deviated significantly from that expected from a population in Hardy-Weinberg equilibrium. Thrombophilia was significantly less frequent in patients with pre-HSVT (250/437, 57.2%) than in patients with post-HSVT (44/45, 97.8%). Conclusions: Our study shows the significant prevalence of PAI-1 4G-4G and MTHFR 677TT in SVT, mainly in post-HSVT. ( J CLIN EXP HEPATOL 2016;6:10-14)

show abstract

Section: Discussionmentioning

confidence: 62%

PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and Prothrombin 20210A in Splanchnic Vein Thrombosis: Analysis of Individual Patient Data From Three Prospective Studies

Pasta¹,

Pasta

D’Amico

2016

Journal of Clinical and Experimental Hepatology

View full text Add to dashboard Cite

show abstract

“…PAI-1 overexpression may compromise normal fibrin clearance mechanisms and promote pathological fibrin deposition and thrombotic events. A polymorphism of this gene, located in the promoter region (at starting position -675, 4G/5G), has previously been associated to CV disease and venous thrombotic episodes [65] in the general population. In patients with RA, this variant, together with TNFRII and FXIIIA, have also been associated with CVD in a cohort of Sweden patients [66].…”

Section: Genetic Influence In the Development Of CV Disease In Patienmentioning

confidence: 99%

Atherosclerosis in Patients with Rheumatoid Arthritis

Zeng¹

2013

Rheumatology (Sunnyvale)

View full text Add to dashboard Cite

Wu et al., Rheumatol Curr Res 2013, S5 http://dx.doi.org/10.4172/2161-1149 Review ArticleOpen Access AbstractBoth Rheumatoid Arthritis (RA) and atherosclerosis are complex polygenic diseases. Previous studies have demonstrated that patients with RA are associated with up to 60% increased risk of cardiovascular disease related death. Nonetheless, the increased cardiovascular morbidity and mortality in patients with RA cannot be entirely explained by traditional risk factors, and likely to be multifactorial. The present article reviews the data supporting the association of RA with cardiovascular risk factors, possible mechanism for developing atherosclerosis and evaluates the potential strategies that may prevent premature atherosclerosis in these patients.

show abstract

“…It has been estimated that between 1990 and 2020, ischemic heart disease alone will increase by 29% in men and 48% in women in developed countries and by 120% in women and 127% in men in developing countries (1). Several factors, including blood pressure, high plasma lipids, smoking, diabetes mellitus, and age, are involved in development of CAD and treatment of these risk factors reduces the rate of mortality (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

“…It has also been reported that high levels of serpin E1 are associated with vascular wall impairment and endothelial dysfunction. Moreover, a cross-sectional case-control study indicated that elevated plasma serpin E1 activity was related to intima-media thickness of carotid arteries (4). Human PAI-1 gene is located at chromosome 7q22, and various genetic polymorphisms have been identified in its promoter region (4).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, a cross-sectional case-control study indicated that elevated plasma serpin E1 activity was related to intima-media thickness of carotid arteries (4). Human PAI-1 gene is located at chromosome 7q22, and various genetic polymorphisms have been identified in its promoter region (4). A common insertion/deletion of guanine has been detected in this region (2).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Association between PAI-1 Gene Promoter Polymorphism and Serum Serpin E1, MDA, and Hs-CRP Levels in Coronary Artery Disease

Karimian

Farajnia

Ghojazadeh

et al. 2016

Int Cardiovasc Res J

View full text Add to dashboard Cite

A B S T R A C TBackground: Coronary artery disease (CAD) caused by atherosclerosis. Studies have shown that there are a number of factors which are closely related to the development and progression of CAD that include Cellular binding molecules like Plasminogen Activator Inhibitor-1(PAI-1), Lipid peroxidation, inflammation and hemostasis. Objectives: The present case-control study aimed to evaluate the association between Plasminogen Activator Inhibitor-1 (PAI-1) 4G/5G polymorphism and oxidative stress markers and Coronary Artery Disease (CAD). Patients and Methods: Blood was drawn and DNA was extracted from 90 subjects (46 patients with angiographically diagnosed CAD and 44 age-and sex-matched healthy controls). The 4G/5G polymorphism of PAI-1 was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis. Besides, the risk factors, serpin E1, Malondialdehyde (MDA), high-sensitivity C-Reactive Protein (hs-CRP), and lipid profile serum levels were measured by standard methods and were compared between the two study groups using independent samples t-test, one-way ANOVA, and Mann-Whitney U test as appropriated. Results: Results: The frequency of 4G/4G genotype of PAI-1 gene was higher in the CAD patients than in the controls (28/46 (60.87%) vs. 8/44 (18.18%), P < 0.01). Additionally, the serpin E1 plasma level was significantly higher in the CAD group carrying the 4G allele compared to those homozygous for the 5G allele (P = 0.016). Besides, a significant difference was found between the 4G/4G and 5G/5G subjects of the CAD group regarding plasma High-Density Lipoprotein (HDL) (P < 0.01). Also, significant differences were observed among the three genotypes of both groups concerning the plasma levels of cholesterol, triglyceride, and Low-Density Lipoprotein (LDL). However, no significant correlation was found between PAI-1 gene polymorphism and MDA serum level, hs-CRP, and risk of CAD. Conclusion: The findings of this study suggested that 4G/4G PAI-1 polymorphism was associated with cholesterol, triglyceride, LDL, and HDL levels and could be regarded as a biomarker for risk of CAD. Our findings suggested that the 4G/5G polymorphism of the PAI-1 gene seems to be a useful marker of fibrinolytic activity. Besides, this polymorphism might contribute to defective fibrinolytic activity due to elevated PAI-1 plasma level, eventually increasing the risk of coronary artery disease. Moreover, the study results demonstrated that this genetic variation might be important in correlation with some other factors, such as increased or decreased triglyceride, cholesterol, and LDL and HDL levels. However, no significant correlation was observed between PAI-1 4G/5G gene polymorphism and serum levels of stress oxidative factors, such as MDA and hs-CRP.

show abstract

The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk

Cited by 93 publications

References 51 publications

PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and Prothrombin 20210A in Splanchnic Vein Thrombosis: Analysis of Individual Patient Data From Three Prospective Studies

PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and Prothrombin 20210A in Splanchnic Vein Thrombosis: Analysis of Individual Patient Data From Three Prospective Studies

Atherosclerosis in Patients with Rheumatoid Arthritis

The Association between PAI-1 Gene Promoter Polymorphism and Serum Serpin E1, MDA, and Hs-CRP Levels in Coronary Artery Disease

Contact Info

Product

Resources

About