The −33T → C Polymorphism in Intron 7 of the TFPI Gene Influences the Risk of Venous Thromboembolism, Independently of the Factor V Leiden and Prothrombin Mutations

Nejma Ameziane; Cendrine Seguin; Delphine Borgel; Frédéric Fumeron; Didier Moatti; Martine Alhenc-Gelas; Bernard Grandchamp; Martine Aiach; Joseph Emmerich; Dominique de Prost

doi:10.1055/s-0037-1613186

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 88(02): 195-199
DOI: 10.1055/s-0037-1613186

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Schattauer GmbH

The −33T → C Polymorphism in Intron 7 of the TFPI Gene Influences the Risk of Venous Thromboembolism, Independently of the Factor V Leiden and Prothrombin Mutations

Nejma Ameziane

¹INSERM 479, Faculté Xavier Bichat, Paris

²Hôpital Louis Mourier, AP-HP, Colombes

,

Cendrine Seguin

¹INSERM 479, Faculté Xavier Bichat, Paris

,

Delphine Borgel

³INSERM 428, Paris

,

Frédéric Fumeron

⁴Service de Nutrition Humaine, Faculté Xavier Bichat, Paris

,

Didier Moatti

¹INSERM 479, Faculté Xavier Bichat, Paris

,

Martine Alhenc-Gelas

³INSERM 428, Paris

⁵Service d'Hématologie Biologique A, Hôpital Européen Georges Pompidou, AP-HP, Paris

,

Bernard Grandchamp

⁷Biochimie Hormonale et Génétique, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France

,

Martine Aiach

³INSERM 428, Paris

⁵Service d'Hématologie Biologique A, Hôpital Européen Georges Pompidou, AP-HP, Paris

,

Joseph Emmerich

³INSERM 428, Paris

⁶Service des Maladies Vasculaires, Hôpital Européen Georges Pompidou, AP-HP, Paris

,

Dominique de Prost

¹INSERM 479, Faculté Xavier Bichat, Paris

²Hôpital Louis Mourier, AP-HP, Colombes

› Author Affiliations

Abstract

Summary

We have previously identified, in intron 7 of the TFPI gene, a T to C single-base polymorphism (−33T→C) which is strongly associated with total circulating TFPI antigen levels. Here we examined the influence of this polymorphism on the risk of venous thromboembolism. The polymorphism was identified in the PATHROS study population (330 cases with venous thromboembolism and 826 controls). The CC genotype was found in 6.4% of cases and 10.2% of controls (age-adjusted odds ratio 0.6; 95% CI 0.3–0.9; p = 0.03). This protective effect persisted after adjustment for oral contraception and the factor V Leiden and prothrombin gene polymorphisms. In 171 controls and 49 cases in whom blood was taken at least three months after the thrombotic event, the CC genotype was associated with significantly higher total TFPI levels than the TT genotype. These results suggest that the CC genotype of the TFPI intron 7 polymorphism is an independent protective factor for venous thromboembolism, an effect probably mediated by increased TFPI levels.

Keywords

TFPI - venous thrombosis - genetic risk factors

Full Text

References

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