The Factor V Gene A4070G Mutation and the Risk of Venous Thrombosis

Martine Alhenc-Gelas; Viviane Nicaud; Sophie Gandrille; Patrick van Dreden; Jean Amiral; Marie-Laurence Aubry; Jean-Noël Fiessinger; Joseph Emmerich; Martine Aiach

doi:10.1055/s-0037-1614441

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 81(02): 193-197
DOI: 10.1055/s-0037-1614441

Review Articles

Schattauer GmbH

The Factor V Gene A4070G Mutation and the Risk of Venous Thrombosis

Martine Alhenc-Gelas

¹From Laboratoire d'Hémostase, Service de Médecine Vasculaire, Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Unité INSERM 428 and Unité INSERM 258, Hôpital Broussais – AP-HP, Paris, France, and Société Serbio, Gennevilliers, France

,

Viviane Nicaud

¹From Laboratoire d'Hémostase, Service de Médecine Vasculaire, Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Unité INSERM 428 and Unité INSERM 258, Hôpital Broussais – AP-HP, Paris, France, and Société Serbio, Gennevilliers, France

,

Sophie Gandrille

¹From Laboratoire d'Hémostase, Service de Médecine Vasculaire, Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Unité INSERM 428 and Unité INSERM 258, Hôpital Broussais – AP-HP, Paris, France, and Société Serbio, Gennevilliers, France

,

Patrick van Dreden

¹From Laboratoire d'Hémostase, Service de Médecine Vasculaire, Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Unité INSERM 428 and Unité INSERM 258, Hôpital Broussais – AP-HP, Paris, France, and Société Serbio, Gennevilliers, France

,

Jean Amiral

¹From Laboratoire d'Hémostase, Service de Médecine Vasculaire, Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Unité INSERM 428 and Unité INSERM 258, Hôpital Broussais – AP-HP, Paris, France, and Société Serbio, Gennevilliers, France

,

Marie-Laurence Aubry

¹From Laboratoire d'Hémostase, Service de Médecine Vasculaire, Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Unité INSERM 428 and Unité INSERM 258, Hôpital Broussais – AP-HP, Paris, France, and Société Serbio, Gennevilliers, France

,

Jean-Noël Fiessinger

¹From Laboratoire d'Hémostase, Service de Médecine Vasculaire, Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Unité INSERM 428 and Unité INSERM 258, Hôpital Broussais – AP-HP, Paris, France, and Société Serbio, Gennevilliers, France

,

Joseph Emmerich

¹From Laboratoire d'Hémostase, Service de Médecine Vasculaire, Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Unité INSERM 428 and Unité INSERM 258, Hôpital Broussais – AP-HP, Paris, France, and Société Serbio, Gennevilliers, France

,

Martine Aiach

¹From Laboratoire d'Hémostase, Service de Médecine Vasculaire, Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Unité INSERM 428 and Unité INSERM 258, Hôpital Broussais – AP-HP, Paris, France, and Société Serbio, Gennevilliers, France

› Author Affiliations

Abstract

Summary

The A4070G polymorphism in exon 13 of the factor V (FV) gene, which replaces His by Arg at position 1299 of the B domain, was recently shown to influence circulating FV levels and to contribute to the activated protein C (APC) resistance phenotype. We examined the impact of this polymorphism in a population of unselected patients with venous thromboembolic disease (VTE). The prevalence of the G4070 (R2) allele was determined in 205 patients and 394 healthy subjects of similar age and sex distribution. Thirty-seven patients (18%) were heterozygous for the R2 allele and 1 (0.5%) was homozygous. Forty-four controls (11.2%) were heterozygous for the R2 allele and 1 (0.2%) was homozygous. Thus, the allelic frequency was significantly higher in the patients with VTE than in the healthy controls, with respective values of 9.5% and 5.8%. The odds ratio was 1.8 (95% CI: 1.1-2.8, p = 0.02), pointing to an increased risk of VTE in carriers of the R2 allele. After excluding subjects with putative or confirmed gene defects (mainly the FV R506Q mutation), the R2 allele was still a risk factor for VTE in the remaining patients, with an odds ratio of 2.0 (95% CI: 1.2-3.5, p = 0.01), demonstrating that this polymorphism is itself a risk factor. This study also confirms that the R2 allele influences APC resistance (APCR) in the absence of the FV R506Q mutation.

Full Text

References

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