Factor VII gene polymorphism, factor VII levels, and prevalent cardiovascular disease - The Framingham Heart Study

Elevated factor VII levels have been associated with increased cardiovascul ar risk in some studies. The arginine/glutamine (Arg/Gln) polymorphism of t he factor VII gene has been previously shown to modify factor VII levels. H owever, the presence of a gene/environment interaction on factor VII levels or a link with cardiovascular disease (CVD) remains uncertain, We studied subjects from the Framingham Heart Study to determine (1) the extent to whi ch this genetic polymorphism affects factor VII levels; (2) whether interac tions exist between this polymorphism and environmental factors on factor V II levels; and (3) the association between the polymorphism and CVD, Genoty pe data and factor VII antigen levels were available in 1816 subjects. Fact or VII levels differed significantly among genotypes in an additive fashion : Gin homozygous, 82.7+/-2.5%; heterozygous, 92.2+/-0.7%; and Arg homozygou s, 100.5+/-0.4% (P<0.0001). The polymorphism was the strongest, single pred ictor of factor VII levels, explaining 7.7% of the total variance of factor VII levels, whereas other traditional risk factors combined explained an a dditional 11.5% of the variance. There was an interaction (P=0.02) between the genotype and total cholesterol on factor VII levels, such that the corr elation coefficient and slope (factor VII level/total cholesterol) were gre atest in Gln/Gln subjects. Among 3204 subjects characterized for genotype a nd CVD, there was no significant relationship between the genotype and CVD (P=0.12), In the Framingham Heart Study, the Arg/Gln polymorphism was signi ficantly associated with factor VII antigen levels. The strength of the ass ociation suggests that generic variation plays an important role in determi ning factor VII levels. However, despite being associated with factor VII l evels, the Arg/Gln polymorphism was not associated with prevalent CVD.