The association of alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism in the LITE study.
BACKGROUND
The alpha-fibrinogen Thr312Ala variant has been shown to influence clot structure through increased factor XIII cross-linking and formation of thicker fibrin fibers. However, the effect of this common variant on risk of venous thromboembolism (VTE) is unclear. This paper reports the association between the Thr312Ala variant and VTE in the LITE study.


METHODS
506 cases and 1014 controls frequency matched on age, sex, race, and study were drawn from two prospective studies and included in the analysis. Logistic regression was used to examine the association between Thr312Ala and VTE.


RESULTS
In a logistic regression model minimally adjusted for the matching variables, the Thr312Ala TA and AA genotypes were associated with a significantly higher risk of VTE than the TT genotype (TA OR and 95% confidence interval 1.27 [1.01-1.60], AA OR 1.49 [1.00-2.22]). Associations were similar in analyses of PE and DVT considered separately and across racial and study subgroups. The association between alpha-fibrinogen Thr312Ala and VTE was modified by both BMI and the FXIII Val34Leu variant; the combination of elevated BMI or FXIII Val34Leu with alpha-fibrinogen Thr312Ala conveyed lower odds of VTE than would be expected by an additive or multiplicative model of individual risk factors.


CONCLUSIONS
These results suggest that alpha-fibrinogen Thr312Ala is involved in the pathogenesis of VTE and that its action may be modified by other VTE risk factors.
Rasmussen-Torvik
Laura J
LJ
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, 1300 S. Second St. Suite 300, Minneapolis, MN 55454, USA.
Cushman
Mary
M
Tsai
Michael Y
MY
Zhang
Yan
Y
Heckbert
Susan R
SR
Rosamond
Wayne D
WD
Folsom
Aaron R
AR
D000368:Aged; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D044465:White People / Q000235:genetics
D005340:Fibrinogen