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

INTRODUCTION: The factor XIII Val34Leu (100 G-->T) and beta-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 beta-fibrinogen -455 G/A were analyzed on stored DNA from 511 thrombosis cases and 1028 control subjects without thrombosis during follow up.

RESULTS: The beta-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. beta-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: beta-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. beta-fibrinogen -455 A may attenuate the increased thrombosis risk associated with obesity or factor V Leiden.