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

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

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20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)339-345
Number of pages7
JournalThrombosis Research
Volume121
Issue number3
DOIs
StatePublished - 2007

Bibliographical note

Funding Information:
The authors thank the participants and staff of the CHS and ARIC studies for their contributions over many years, and Ching Ping Hong for analytic assistance. A full list of participating CHS investigators and institutions can be found at http://www.chs-nhlbi.org . The Atherosclerosis Risk in Communities Study was funded by contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, and the Cardiovascular Health Study was funded by contracts N01-HC-85079 to N01-HC-85086 from the National Heart, Lung, and Blood Institute. The LITE study was funded by R01 HL59367 from the National Heart, Lung, and Blood Institute. National Heart, Lung, and Blood Institute investigators were involved in the design and acquisition of data for the ARIC and CHS studies, but not the LITE study.

Keywords

  • Factor V Leiden
  • Factor XIII
  • Fibrinogen
  • Obesity
  • Risk factor
  • Venous thrombosis

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