Factor VII coagulant activity, factor VII -670A/C and -402G/A polymorphisms, and risk of venous thromboembolism.
BACKGROUND
Most epidemiological studies have found no association between levels of factor (F) VII:C and venous thromboembolism (VTE). Our Longitudinal Investigation of Thromboembolism Etiology (LITE) had, in contrast, reported an independent, increased risk of VTE after 7.8 years of follow-up for those with high baseline levels of FVII:C.


OBJECTIVE
To confirm whether FVII:C is associated with VTE after 12.6 years of follow-up and to examine whether two FVII gene polymorphisms (-670A/C and -402G/A) are related to VTE occurrence.


METHODS
In 19 091 LITE participants with no prior history of VTE or cancer, we measured FVII:C at baseline and identified 404 new VTEs. We also performed a nested case-control study to relate the polymorphisms to VTE (n = 490 without exclusion for cancer or prior VTE).


RESULTS
FVII:C was not independently associated with VTE occurrence after extended follow-up. Multivariable-adjusted rate ratios for VTE were 1.00, 1.00, 0.94, 1.00, and 1.38 (P-trend = 0.48) for the <25th, 25th-49th, 50th-74th, 75th-94th, and >or=95th percentiles of FVII:C, respectively. The -670C and -402A alleles were in high linkage disequilibrium, and both were associated with greater FVII:C levels. However, neither polymorphism was associated with VTE occurrence.


CONCLUSIONS
After extended follow-up, LITE offers little evidence that a greater FVII level is a risk factor for VTE.
Folsom
A R
AR
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55454-1015, USA. folsom@epi.umn.edu
Cushman
M
M
Heckbert
S R
SR
Ohira
T
T
Rasmussen-Torvik
L
L
Tsai
M Y
MY
D000483:Alleles; D000941:Antigens / Q000737:chemistry*; D003029:Coagulants / Q000737:chemistry*; D005167:Factor VII / Q000737:chemistry* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D013923:Thromboembolism / Q000188:drug therapy / Q000235:genetics* / Q000517:prevention & control; D020246:Venous Thrombosis / Q000188:drug therapy / Q000235:genetics* / Q000517:prevention & control
D000941:Antigens; D003029:Coagulants; C042580:factor VII clotting antigen; D005167:Factor VII