ELEVATED LEVELS OF FACTOR-VII ACTIVITY IN THE POSTPRANDIAL STATE - EFFECT OF THE FACTOR-VII ARG-GLN POLYMORPHISM

A genetic polymorphism (Arg/Gln(353)) of coagulation factor VII was re cently identified and shown to be associated with differences in basal factor VII coagulant activity. Postprandial lipaemia seems to exert a n acute but evanescent effect on the activity of factor VII, and the i nfluence of the Arg/Gln(353) polymorphism on factor VII activation dur ing postprandial lipaemia was therefore studied in male post-infarctio n patients [age 48.8 +/- 3.3 years (mean +/- SD)] with Arg/Arg (n = 23 ) and Arg/Gln (n = 8) genotypes. Factor VII antigen (VIIag) and activi ty along with plasma lipoproteins were determined before and after int ake of a mixed meal-type of oral fat load. Patients with the Arg/Gln g enotype had basal VIIag and activated factor VII (VIIa) levels 75% and 48%, respectively, of those of patients homozygous for the Arg allele . In absolute terms, VIIa increased more in homozygotes for the Arg al lele (Delta 0-6 h VIIa 1.76 +/- 1.48 ng/ml) than in heterozygotes (0.6 0 +/- 0.27 ng/ml) in response to fat intake, but the percentage increa se in VIIa molecules did not differ significantly between subjects wit h Arg/Arg and Arg/Gln genotypes (37 +/- 32% versus 27 +/- 15%). This s uggests that the influence of the Arg/Gln polymorphism on factor VII a ctivity is mainly accounted for by differences in the basal factor VII protein level between genotypes. Since most of our lives are spent in the postprandial state, possession of the factor VII-Gln(353) allele is likely to confer protection against coronary heart disease by reduc ing the amount of VIIa produced in response to fat intake.