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Tissue plasminogen activator genetic polymorphisms do not influence tissue plasminogen activator release in patients with coronary heart disease
Author(s) -
ROBINSON S. D.,
LUDLAM C. A.,
BOON N. A.,
NEWBY D. E.
Publication year - 2006
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2006.02124.x
Subject(s) - tissue plasminogen activator , plasminogen activator , medicine , coronary heart disease , cardiology , activator (genetics) , receptor
Summary. 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). 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. 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). 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.