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The influence of alpha-2-antiplasmin polymorphism Arg6Trp on fibrinolysis; the leeds family study
Abstract number: PP-WE-231
Uitte de Willige1 S., Carter1 A.M., Standeven1 K.F., Philippou1 H., Grant1 P.J., Ariëns1 R.A.S.
11Division of Cardiovascular and Diabetes Research, University of Leeds, Leeds, UK
How-to-cite Uitte de Willige S, Carter AM, Standeven KF, Philippou H, Grant PJ, Ariëns RAS. The influence of alpha-2-antiplasmin polymorphism Arg6Trp on fibrinolysis; the leeds family study. Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract PP-WE-231
The main inhibitor of plasmin, alpha-2-antiplasmin (α2AP), is secreted into plasma as a 70 kDa protein of 464 amino acids. During circulation in plasma, proteolytic cleavage between Pro12-Asn13 results in a 452 amino acid version with Asn at the N-terminus. In vitro this shortened version has been shown to be crosslinked into fibrin about 13 times faster than full length α2AP and increases plasma clot lysis time (PCLT). A polymorphism at position 6, Arg6Trp (R6W), has been shown to be related to the percentage of N-terminally cleaved α2AP. Plasma purified R6-α2AP was cleaved about 8-fold faster than W6-α2AP and plasma from W homozygous individuals tended to have shorter PCLTs.
Methods: In this study we genotyped R6W in 531 individuals of the Leeds Family Study in which PCLT had been measured previously. Time to 50% lysis (Lys50MA) was determined as time from maximum absorbance to time at which a 50% reduction in absorbance occurred.
Results: Genotype frequencies were 54.2% RR, 40.9% RW and 4.9% WW, allele frequencies were 74.7% R and 25.3% W. Analysis by SOLAR (taking family structure into account) showed that R6W accounts for approximately 1.3% of variance in lysis time after accounting for age and sex. We confirm that the W-allele associates with shorter PCLT (P = 0.025), with ∼ 10% reduction in PCLT per W-allele in the non-related individuals (n = 96). However, inclusion of fibrinogen level in the model rendered the influence of R6W on Lys50MA not significant (P = 0.187). Entering an interaction term in the model showed significance for the interaction between R6W and fibrinogen level (P = 0.004), suggesting that the influence of R6W on Lys50MA is modulated by fibrinogen level.
Conclusion: α2ap polymorphism R6W influences PCLT; however this influence is modulated by fibrinogen level.
Disclosure of interest: none declared.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
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