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Thromb Haemost 2000; 83(04): 577-582
DOI: 10.1055/s-0037-1613866
DOI: 10.1055/s-0037-1613866
Commentary
The HR2 Haplotype of Factor V: Effects on Factor V Levels, Normalized Activated Protein C Sensitivity Ratios and the Risk of Venous Thrombosis
This study was supported by grant no. 95.001 from the Trombosestichting Nederland. The LETS study was originally supported by a grant from the Netherlands Heart Foundation (89.063). Dr. T. Koster, Mrs T. Visser and Mrs A. Schreijer are acknowledged for their work in contacting the patients and processing the bloodsamples. We are grateful to Dr. F. J. M. van der Meer (Anticoagulation Clinic Leiden), Mrs Dr. L. P. Colly (Anticoagulation Clinic Amsterdam) and Dr. P. H. Trienekens (Anticoagulation Clinic Rotterdam) for their assistence.
Further Information
Publication History
Received
13 September 1999
Accepted after revision
14 December 1999
Publication Date:
08 December 2017 (online)
Summary
We studied the HR2 haplotype of the factor V gene in a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched healthy controls (Leiden Thrombophilia Study, LETS). We investigated both the original His1299Arg (A4070G) polymorphism and the Met385Thr (T1328C) polymorphism. This latter polymorphism, located in exon 8 (heavy chain), is always present in the HR2 haplotype, but also occurs on its own in a His1299 (wt) background. The HR2 haplotype was not associated with an increased risk of venous thrombosis (OR = 1.2, 95% confidence interval: 0.8-2.0). We did not find an association between the HR2 haplotype and a reduced sensitivity for activated protein C (APC) in non-carriers of factor V Leiden (FVL). However, in compound heterozygous FVL/HR2 carriers the sensitivity for APC was reduced. The HR2 haplotype was also associated with reduced factor V antigen levels in both patients and controls. Sequence analysis of the promoter region of factor V in HR2 homozygotes did not reveal any sequence variations that could explain the reduced FV levels. Our results show that the HR2 haplotype is not associated with an increased risk of venous thrombosis or with a reduced sensitivity for APC in non-FVL carriers. However, the HR2 haplotype is associated with a reduced sensitivity for APC in carriers of FVL and with reduced factor V antigen levels.
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