The fibrinogen gamma (FGG) 10034C>T polymorphism is associated with venous thrombosis

doi:10.1016/j.thromres.2007.03.007

Thrombosis Research

Volume 121, Issue 1, 2007, Pages 33-36

https://doi.org/10.1016/j.thromres.2007.03.007 Get rights and content

Abstract

Introduction

Thrombin-induced conversion of fibrinogen to fibrin plays an essential role in hemostasis and results in the stabilization of thrombi. Elevated plasma fibrinogen levels have been associated with both increased plasma viscosity and platelet aggregability. Recently, a haplotype-tagging single nucleotide polymorphism characterized by a C to T substitution at nucleotide 10034 of the fibrinogen gamma gene (FGG 10034C>T, rs2066865), has been proposed as a novel risk factor for deep venous thrombosis (DVT). Aim of the present study was to provide further data on the role of the FGG 10034C>T polymorphism for DVT.

Materials and methods

FGG genotypes were determined by 5′-exonuclease assay (TaqMan) in 358 patients with documented DVT and a total of 783 control subjects.

Results

In a multivariate analysis adjusting for age, sex, presence of factor V Leiden and carriage of prothrombin 20210A, homozygosity for the FGG 10034 TT genotype yielded an odds ratio of 2.01 (95% CI 1.23–3.31; p = 0.006) for DVT.

Conclusions

Our data confirm the primary finding that the FGG 10034C>T polymorphism is associated with DVT risk.

Introduction

Deep venous thrombosis (DVT) is a multifactorial disease with both environmental and genetic factors contributing to its development [1], [2]. Elevated plasma fibrinogen concentrations have previously been associated with an increased risk for DVT [3], [4]. Fibrinogen is a 340 kDa plasma glycoprotein and consists of three pairs of non-identical polypeptide chains (Aα, Bβ, and γ), which are each encoded by a different gene (fibrinogen alpha [FGA], fibrinogen beta [FGB] and fibrinogen gamma [FGG]) [5], [6], [7], [8]. Thrombin-induced conversion of fibrinogen to fibrin plays an essential role in hemostasis and results in stabilization of the thrombus. Furthermore, elevated plasma fibrinogen levels have been associated with both increased plasma viscosity and platelet aggregability [9], [10].

A haplotype-tagging single nucleotide polymorphism (htSNP) characterized by a C to T substitution at nucleotide 10034 of the FGG gene (FGG 10034C>T, rs2066865), has recently been proposed as a novel risk factor for DVT in the Leiden Thrombophilia Study [11]. The purpose of the present study was re-analyzed by the previously described association between the FGG 10034C>T polymorphism and DVT in an Austrian population.

Section snippets

Materials and methods

Three hundred and fifty eight subjects with a documented episode of DVT of the lower extremities, admitted to the Department of Internal Medicine, Medical University Graz, between December 1997 and June 2002, were enrolled as the patient group [12]. DVT was diagnosed by ultrasonography and/or venography. Pulmonary embolism (PE) was diagnosed by ventilation–perfusion scintigraphy and/or CT pulmonary angiography. Patients with isolated PE without diagnosis of DVT were not eligible.

A control group

Results

Characteristics of study subjects are summarized in Table 1. DVT was diagnosed as first event in 299 (83.5%) patients and recurrent event in 59 (16.5%) patients. FGG genotypes were determined successfully in 341 (95.3%) patients with DVT, 342 (96.6%) in-house controls and all population-based controls and did not deviate from the Hardy–Weinberg equilibrium among either group. Genotype distributions are summarized in Table 1.

Genotype frequencies were almost identical among in-house controls and

Discussion

In the present study, homozygous carriers of the FGG 10034T-allele were found more often in patients with DVT than among control subjects without thrombosis. Our result confirms the primary finding of Uitte de Willige and coworkers, who identified this genotype as a novel risk factor for DVT [11] (Fig. 1).

The precise mechanism by which this polymorphism affects susceptibility to DVT has only partially been determined. According to SeattleSNPs (http://pga.gs.washington.edu), the genetic

Acknowledgments

We thank Biomedical Scientists Manuela Gutjahr, Renate Jahrbacher and Olivia Trummer for helpful comments and critical evaluation of the manuscript.

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¹: These authors contributed equally to the study.

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REGULAR ARTICLEThe fibrinogen gamma (FGG) 10034C>T polymorphism is associated with venous thrombosis

Abstract

Introduction

Materials and methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgments

J Thromb Haemost

J Thromb Haemost

J Thromb Haemost

Blood

J Thromb Haemost

Thromb Res

J Biol Chem

REGULAR ARTICLE
The fibrinogen gamma (FGG) 10034C>T polymorphism is associated with venous thrombosis