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Tissue plasminogen activator genetic polymorphisms do not influence tissue plasminogen activator release in patients with coronary heart disease.
- Source :
-
Journal of thrombosis and haemostasis : JTH [J Thromb Haemost] 2006 Oct; Vol. 4 (10), pp. 2262-9. Date of Electronic Publication: 2006 Jul 12. - Publication Year :
- 2006
-
Abstract
- Objectives: To determine if polymorphisms of the tissue plasminogen activator (t-PA) gene influence acute endogenous t-PA release in patients with coronary heart disease (CHD).<br />Methods: Forearm blood flow and plasma t-PA concentrations were measured in response to intra-brachial infusion of substance P and sodium nitroprusside in 96 patients with stable CHD. Genotyping was performed using a Taqman polymerase chain reaction assay specifically designed to detect the polymorphisms of interest: (i) Alu-repeat insertion/deletion sequence; (ii) C-->T substitution in an upstream enhancer region (-7351 C/T); (iii) T-->C in exon 6 (20 099 T/C); and (iv) T-->A (27 445 T/A) in intron 10.<br />Results: Substance P and sodium nitroprusside caused dose-dependent increases in forearm blood flow in all patients (P < 0.001 for all) that were independent of the four genetic polymorphisms. Similarly, there were no differences in basal plasma t-PA antigen concentrations or net t-PA release between genotypes. Compared to non-smokers, smokers exhibited impaired substance P-induced vasodilatation (P < 0.001) and t-PA release (P = 0.05).<br />Conclusions: Despite confirming our previous findings in cigarette smokers, we have found no effect of polymorphisms of the t-PA gene on two complementary aspects of endothelial function. We conclude that genetic variation of the t-PA locus is unlikely to have a major influence on acute t-PA release in subjects with established CHD.
- Subjects :
- Aged
Female
Fibrinolysis genetics
Gene Deletion
Genotype
Humans
Male
Middle Aged
Nitroprusside pharmacology
Substance P pharmacology
Tissue Plasminogen Activator physiology
Coronary Disease genetics
Coronary Disease pathology
Polymorphism, Genetic
Tissue Plasminogen Activator genetics
Tissue Plasminogen Activator metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7933
- Volume :
- 4
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of thrombosis and haemostasis : JTH
- Publication Type :
- Academic Journal
- Accession number :
- 16836660
- Full Text :
- https://doi.org/10.1111/j.1538-7836.2006.02124.x