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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:593.)
© 2000 American Heart Association, Inc.

Thrombosis

Factor VII Gene Polymorphism, Factor VII Levels, and Prevalent Cardiovascular Disease

The Framingham Heart Study

DaLi Feng; Geoffrey H. Tofler; Martin G. Larson; Christopher J. O’Donnell; Izabella Lipinska; Christian Schmitz; Patrice A. Sutherland; Michael T. Johnstone; James E. Muller; Ralph B. D’Agostino; Daniel Levy; Klaus Lindpaintner

From the Institute for Prevention of Cardiovascular Disease, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (D.L.F., I.L., M.T.J.); Royal North Shore Hospital, Sydney, Australia (G.H.T.); the National Heart, Lung, and Blood Institute Framingham Heart Study, Framingham (M.G.L., C.J.O’D., P.A.S., D.L.); the Cardiovascular Division, Brigham & Women’s Hospital, Harvard Medical School, Boston (C.S., K.L.); Massachusetts General Hospital, Harvard Medical School, Boston (J.E.M.); and the Department of Mathematics (R.B.D’A.), Boston University, Boston, Mass.

Correspondence to Klaus Lindpaintner, MD, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St—Thorn 1203, Boston, MA 02115-6195. E-mail KL{at}Calvin.BWH.Harvard.edu

Abstract—Elevated factor VII levels have been associated with increased cardiovascular risk in some studies. The arginine/glutamine (Arg/Gln) polymorphism of the factor VII gene has been previously shown to modify factor VII levels. However, 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 which this genetic polymorphism affects factor VII levels; (2) whether interactions exist between this polymorphism and environmental factors on factor VII levels; and (3) the association between the polymorphism and CVD. Genotype data and factor VII antigen levels were available in 1816 subjects. Factor VII levels differed significantly among genotypes in an additive fashion: Gln homozygous, 82.7±2.5%; heterozygous, 92.2±0.7%; and Arg homozygous, 100.5±0.4% (P<0.0001). The polymorphism was the strongest, single predictor of factor VII levels, explaining 7.7% of the total variance of factor VII levels, whereas other traditional risk factors combined explained an additional 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 correlation coefficient and slope (factor VII level/total cholesterol) were greatest in Gln/Gln subjects. Among 3204 subjects characterized for genotype and CVD, there was no significant relationship between the genotype and CVD (P=0.12). In the Framingham Heart Study, the Arg/Gln polymorphism was significantly associated with factor VII antigen levels. The strength of the association suggests that genetic variation plays an important role in determining factor VII levels. However, despite being associated with factor VII levels, the Arg/Gln polymorphism was not associated with prevalent CVD.

Key Words: factor VII • genetics • polymorphisms • cardiovascular disease • risk factors

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