Coagulation factor V G allele and HR2 haplotype: factor V activity, activated protein C resistance and risk of venous thrombosis.

Abstract

Factor V Leiden is a well-known risk factor for venous thrombosis. The dual role of factor V as a coagulatory and anticoagulatory cofactor permits the assumption that further mutations in the factor V gene are of importance in the study of the risk of thrombosis. Relevant studies to date have given rise to a controversy over this risk for the HR2 haplotype. For the G allele, defined in our work group as a G at the nucleotide positions 2391, 2663, 2684 and 2863, there have been to date no other investigations of thrombotic risk. In a case-control study on 347 patients with deep venous thrombosis (DVT) and 282 controls, we investigated the association of the HR2 haplotype and the G allele with DVT. We found no association between HR2 haplotype and DVT [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.58-1.30; P = 0.537]. The frequency of the G allele was, on the contrary, higher in the control group than among the patients (OR 0.68, 95% CI: 0.53 to 0.89; P = 0.005). The factor V activity of the HR2 carriers was lower than that of the wild type and G allele carriers. The HR2 haplotype exhibited a moderate influence on activated protein C response. This study presented no evidence of thrombotic risk for the HR2 haplotype alone. The results here permit the assumption of a protective effect of the G allele. The source of a possible protective influence of the G allele on thrombotic risk is at present unclear.

• Authors: Heike Kostka, Thomas Schwarz, Sebastian Schellong, Cornelia Mix, Eberhard Kuhlisch, Theodora Temelkova-Kurktschiev, Elena Henkel, Carsta Köhler, Siegmund Gehrisch, Gabriele Siegert
• Journal: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis (Blood Coagul Fibrinolysis) Vol. 14 Issue 1 Pg. 49-56 (Jan 2003) ISSN: 0957-5235 [Print] England
• PMID: 12544728 (Publication Type: Journal Article)
• Copyright: Copyright 2003 Lippincott Williams & Wilkins

Chemical References

• Guanine
• Factor V

Topics

• Activated Protein C Resistance (etiology)
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Alleles
• Case-Control Studies
• Factor V (genetics, metabolism)
• Female
• Gene Frequency
• Guanine
• Haplotypes
• Humans
• Male
• Middle Aged
• Odds Ratio
• Polymorphism, Single Nucleotide (physiology)
• Risk Factors
• Venous Thrombosis (etiology, genetics)