title: 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.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Hospital, Technical University of Dresden, Dresden, Germany. hk1@rcs.urz.tu-dresden.de
authors.forename: Heike
authors.initials: H
authors.lastname: Kostka
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schellong
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mix
authors.forename: Eberhard
authors.initials: E
authors.lastname: Kuhlisch
authors.forename: Theodora
authors.initials: T
authors.lastname: Temelkova-Kurktschiev
authors.forename: Elena
authors.initials: E
authors.lastname: Henkel
authors.forename: Carsta
authors.initials: C
authors.lastname: Köhler
authors.forename: Siegmund
authors.initials: S
authors.lastname: Gehrisch
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siegert
mesh_terms: D020016:Activated Protein C Resistance / Q000209:etiology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D006147:Guanine; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D012307:Risk Factors; D020246:Venous Thrombosis / Q000209:etiology / Q000235:genetics*
chemical_list: D006147:Guanine; D005165:Factor V