Factor VII Gene Polymorphisms Contribute About One Third of the Factor VII Level Variation in Plasma

TLDR

The study assessed how genetic variation in the factor VII gene—specifically the 5′F7, IVS7 intronic, and 353 Arg‑Gln polymorphisms—affects plasma factor VII activity and antigen levels. The polymorphisms studied were strongly associated with factor VII levels, with 5′F7 and 353 Arg‑Gln explaining similar portions of variance, IVS7 contributing less, and combined genotypes accounting for up to 40 % of phenotypic variation; using two markers is recommended, and the 5′F7 marker can be detected by a simple immunoassay, while activity and antigen levels varied similarly, underscoring the genetic influence on plasma FVII and hemostatic balance. Published in Arteriosclerosis, Thrombosis, and Vascular Biology, 1996;16:72‑75.

Abstract

To assess the role of genetic variation in determining factor VII (FVII) activity and antigen levels we studied a polymorphism located in the 5′ region of the gene (5′F7), an intronic mutation (IVS7), and the 353 Arg-Gln polymorphism. All the polymorphisms, which showed strong allelic association, analyzed separately or in combination by the one-way analysis of variance, were associated with significantly different FVII levels. The 5′F7 and 353 Arg-Gln polymorphic systems, which have very similar allele frequencies, contributed to a similar extent to the total phenotypic variance, whereas the contribution of the IVS7 polymorphism was lower. Genetic variation at the FVII locus, evaluated on combined genotypes, accounted for up to 40% of the phenotypic FVII variance. As also shown by the two-way analysis of variance, the use of two out of three markers is advisable, and since the 5′F7 polymorphism can be screened by a simple immunoassay, it should be preferred for population-based studies. No substantial differences between FVII activity and FVII antigen levels were found, thus suggesting that the variation was due to biosynthesis- or stabilitymediated mechanisms. The genetic control of FVII levels described in this study plays an important role in determining plasma FVII level variability, which may influence the hemostatic balance. (Arterioscler Thromb Vase Biol. 1996;16:72-75.)