Associations of the β-fibrinogen Hae III and factor XIII Val34Leu gene variants with venous thrombosis

Cushman, Mary; Cornell, Alexandra; Folsom, Aaron R.; Wang, Lu; Tsai, Michael Y.; Polak, Joseph; Tang, Zhonghua

doi:10.1016/j.thromres.2007.05.009

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Volume 121, Issue 3 , Pages 339-345, 2007

Associations of the β-fibrinogen Hae III and factor XIII Val34Leu gene variants with venous thrombosis

Mary Cushman
- Department of Medicine, University of Vermont College of Medicine, Burlington, VT, USA
- Corresponding author. Department of Medicine, University of Vermont, 208 South Park Drive, Suite 2, Colchester, VT 05446, USA. Tel.: +1 802 656 8968; fax: +1 802 656 8965.
Alexandra Cornell
- Department of Medicine, University of Vermont College of Medicine, Burlington, VT, USA
Aaron R. Folsom
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA
Lu Wang
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
Michael Y. Tsai
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
Joseph Polak
- Department of Radiology, New England Medical Center, Boston, MA, USA
Zhonghua Tang
- Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, USA

Received 2 April 2007; received in revised form 9 May 2007; accepted 14 May 2007.

Abstract

Introduction

The factor XIII Val34Leu (100 G→T) and β-fibrinogen Hae III (−455 G→A) gene variants have been associated with reduced risk of venous thrombosis, but not in all studies.

Methods

We investigated the associations of these polymorphisms with risk of venous thrombosis in a prospective, population-based study of 21,680 men and women aged 45–100 years at enrollment. Factor XIII 100 G/T and β-fibrinogen −455 G/A were analyzed on stored DNA from 511 thrombosis cases and 1028 control subjects without thrombosis during follow up.

Results

The β-fibrinogen A allele was present in 24.4% of cases and 32.3% of controls. Compared to GG subjects, the age, race, and sex adjusted odds ratio (OR) of venous thrombosis was 0.77 (95% CI 0.59–0.99) for GA subjects, and 0.60 (95% CI 0.31–1.16) for AA subjects. The adjusted OR of thrombosis associated with factor XIII 100 G/T was 1.01 (95% CI 0.81–1.26) for GT subjects and 0.45 (95% CI 0.44–1.19) for TT subjects, compared to GG. For both genotypes, ORs of thrombosis were similar in whites and non-whites, although there were no non-white fibrinogen AA cases. β-fibrinogen −455 GA or AA attenuated the thrombosis risk associated with obesity (from 2.14 to 1.25) and factor V Leiden (from 3.89 to 2.36).

Conclusions

β-fibrinogen −455 G/A, but not factor XIII 100 G/T, was associated with a lower risk of venous thrombosis in this general population sample. β-fibrinogen −455 A may attenuate the increased thrombosis risk associated with obesity or factor V Leiden.

Abbreviations: VT, venous thrombosis, OR, odds ratio, LITE, Longitudinal Investigation of Thromboembolism Etiology, CHS, Cardiovascular Health Study, ARIC, Atherosclerosis Risk in Communities, CI, confidence interval, FXIII, factor XIII