Does Low Protein Concentration of Tissue-type Plasminogen Activator Predict a Low Risk of Spontaneous Deep Vein Thrombosis?

Gram, Jørgen Brodersen; Sidelmann, Johannes Jakobsen; Jespersen, Jørgen

doi:10.1055/s-0038-1649803

Cited by 10 publications

(1 citation statement)

References 19 publications

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“…Defective fibrinolysis due to increased PAI-1 is observed in up to 40% of patients with venous thromboembolism (12)(13)(14)(15)(16)(17). Increased PAI-1 correlates also with the development of future thrombotic events (18) and might therefore be causally related to the disease.…”

Section: Discussionmentioning

confidence: 99%

The 4G/5G Sequence Polymorphism in the Promoter of Plasminogen Activator Inhibitor-1 (PAI-1) Gene: Relationship to Plasma PAI-1 Level in Venous Thromboembolism

Stegnar¹,

Uhrín²,

Peternel³

et al. 1998

Thromb Haemost

117

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SummaryImpaired fibrinolysis due to increased plasminogen activator inhibitor-1 (PAI-1) is observed in up to 40% of patients with venous thromboembolism and might be causally related to the disease. There is evidence that genetic variations in the promoter of the PAI-1 gene and metabolic factors contribute to increased plasma PAI-1 levels.A single nucleotide insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene and metabolic factors were studied in 158 unrelated patients below the age of 61 years (43 ± 11 years, mean ± standard deviation) with history of objectively confirmed venous thromboembolism and in 145 apparently healthy controls.Patients had on average two times higher PAI activity (11.9 vs. 6.1 IU/ml) and by 40% higher PAI-1 antigen (14.8 vs. 10.7 ng/ml) than healthy controls, and also higher body mass index, lipid levels, fasting glucose and insulin. Patients differed significantly from healthy controls neither in the frequency of the 4G and 5G alleles (0.57/0.43 in patients and 0.52/0.48 in controls) nor in the distribution of the 4G/5G genotypes. Possession of the 4G/4G or the 4G/5G genotype did not increase relative risk for venous thromboembolic disease and the distribution of the 4G/5G genotypes was neither associated with recurrent nor with spontaneous disease. In patients association between the 4G/5G genotypes and PAI activity (adjusted for body mass index, triglyceride and glucose level) was observed, with the highest PAI activity values in the 4G/4G genotype (14.6 IU/ml), intermediate in the 4G/5G genotype (13.3 IU/ml) and the lowest in the 5G/5G genotype (5.2 IU/ml, all values means). Association between PAI activity and triglyceride level was the strongest in the 4G/4G genotype (correlation coefficient r = 0.47, p <0.01) and the weakest in the 5G/5G genotype (r = -0.04, not significant).In conclusion, the present case-control study shows an association between the 4G/5G polymorphism in the promoter of the PAI-1 gene and plasma PAI-1 levels in patients with venous thromboembolism. Similar distribution of the 4G/5G genotypes in patients and healthy controls suggests that this genetic variation by itself is not a major risk factor for venous thromboembolism.

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Section: Discussionmentioning

confidence: 99%

The 4G/5G Sequence Polymorphism in the Promoter of Plasminogen Activator Inhibitor-1 (PAI-1) Gene: Relationship to Plasma PAI-1 Level in Venous Thromboembolism

Stegnar¹,

Uhrín²,

Peternel³

et al. 1998

Thromb Haemost

117

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Relationship of venous thromboembolism and myocardial infarction with the renin‐angiotensin system in African‐Americans

et al. 2002

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Genetic polymorphisms/mutations associated with venous thrombosis have largely been con®ned to the genes that encode for proteins in either the coagulant or the anticoagulant pathway. Although genetic alterations in the renin±angiotensin system have been reported to have a role in myocardial infarction and hypertension, there is recent evidence to suggest that there may also be an association with venous thrombosis. To extend our earlier observation of an association between the ACE DD genotype in African-American males and venous thrombosis, other genes in the renin±angiotensin pathway were investigated for possible disease association and were compared with African-Americans with myocardial infarction. African-American patients with a documented history of venous thrombosis or a history of myocardial infarction were eligible for participation as cases in the study. Control subjects were African-American outpatients attending a clinical laboratory for routine blood tests who had comparable age and gender distributions to the cases. Persons with a history of myocardial infarction, stroke, or thrombosis were excluded. Genes that were analyzed for known polymorphisms included angiotensinogen, angiotensin-converting enzyme (ACE), and the angiotensin II type I receptor. Our results showed that the ACE DD genotype was also associated with MI in African-American males but not in females. Racial/ethnic and sex differences were also found with respect to the genotype distribution of the ACE 4656(CT) 2/3 polymorphism. It was observed that the 2/2 genotype had a protective effective in males for myocardial infarction and venous thrombosis. The data also demonstrated that the allele frequencies of the A1166C variant of the angiotensin II type I receptor were different in African-Americans as compared to Caucasians. Am.

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Factor VII-activating protease in patients with acute deep venous thrombosis

Sidelmann

Vitzthum

Funding

et al. 2008

Thrombosis Research

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Does Low Protein Concentration of Tissue-type Plasminogen Activator Predict a Low Risk of Spontaneous Deep Vein Thrombosis?

Cited by 10 publications

References 19 publications

The 4G/5G Sequence Polymorphism in the Promoter of Plasminogen Activator Inhibitor-1 (PAI-1) Gene: Relationship to Plasma PAI-1 Level in Venous Thromboembolism

The 4G/5G Sequence Polymorphism in the Promoter of Plasminogen Activator Inhibitor-1 (PAI-1) Gene: Relationship to Plasma PAI-1 Level in Venous Thromboembolism

Relationship of venous thromboembolism and myocardial infarction with the renin‐angiotensin system in African‐Americans

Factor VII-activating protease in patients with acute deep venous thrombosis

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