Back
A CODING SNP AT THE GPI-ATTACHMENT SITE IN THE TFPI-BETA-SPECIFIC EXON IS ASSOCIATED WITH TFPI LEVELS
Abstract number: P-T-017
Vos1 H.L., van Hylckama Vlieg2 A., Sandset3 P.M., Rosendaal2 F.R.
11Thrombosis and Haemostasis Research Center 22Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands 33-, Ullevål University Hospital, Oslo, Norway
How-to-cite Vos HL, van Hylckama Vlieg A, Sandset PM, Rosendaal FR. A CODING SNP AT THE GPI-ATTACHMENT SITE IN THE TFPI-BETA-SPECIFIC EXON IS ASSOCIATED WITH TFPI LEVELS. J Thromb Haemost 2007; 5 Supplement 2: P-T-017
Abstract
Introduction: Tissue Factor Pathway Inhibitor (TFPI) is an extracellular inhibitor of coagulation that is found on membranes. Two isoforms are generated by alternative mRNA processing; TFPIalpha has 7 coding exons, whereas TFPIbeta is encoded by 6 exons. The last TFPIbeta exon replaces the last two TFPIalpha exons. The TFPIbeta-specific exon encodes an Asn-residue enabling membrane attachment of TFPIbeta via a GPI-(glycosylphosphatidylinositol) anchor. It is replaced by a Ser-residue in carriers of the G-allele of SNP rs7586970. We hypothesized that this might affect TFPI activity or antigen levels or thrombotic risk, although both amino acids may serve in GPI-anchorage.
Methods: The SNP was determined in 468 patients and 471 healthy controls from the Leiden Thrombophilia Study, which contains 474 patients with a first case of deep venous thrombosis (DVT) and 474 controls. Protein variables had been determined previously (ref 1). Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated.
Results: The SNP-alleles were associated with TFPI activity and with total, but not free, TFPI antigen levels in controls. Thus, TFPI activity ranged from 112.6% (CI95 110.5-114.6) in AA-carriers to 128.3% (123.5-133.1) in GG-carriers, total TFPI levels from 63.0 ng/ml (61.4-64.6) to 80.7 ng/ml (75.0-86.4) and free TFPI levels from 12.8 ng/ml (12.2-13.3) to 13.0 ng/ml (11.5-14.4), respectively. No association between this SNP and DVT-risk was found.
Conclusions: SNP rs7586970 is associated with total TFPI antigen levels and with TFPI activity, but not with free TFPI antigen levels and with DVT risk.
References: 1. Dahm A, Van Hylckama Vlieg A, Bendz B, Rosendaal F, Bertina RM, Sandset PM. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis. Blood. 2003;101:4387-92.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
Session Details
| Date: |
01/08/2007
|
| Time: |
00:00-00:00
|
| Session name: |
XXIst ISTH Congress |
| Subject: |
|
| Location: |
Oxford, UK |
| Presentation type: |
|
| Back to top |
|
