Associations of the beta-fibrinogen Hae III and factor XIII Val34Leu gene variants with venous thrombosis.
BACKGROUND
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.
Cushman
Mary
M
Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05446, USA. mary.cushman@uvm.edu
Cornell
Alexandra
A
Folsom
Aaron R
AR
Wang
Lu
L
Tsai
Michael Y
MY
Polak
Joseph
J
Tang
Zhonghua
Z
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood* / Q000235:genetics*
D017931:DNA Primers; D005340:Fibrinogen; D005176:Factor XIII; D015252:Deoxyribonucleases, Type II Site-Specific; C024403:GGCC-specific type II deoxyribonucleases