CONTRIBUTION OF FACTOR-VII GENOTYPE TO ACTIVATED FVII LEVELS - DIFFERENCES IN GENOTYPE FREQUENCIES BETWEEN NORTHERN AND SOUTHERN EUROPEAN POPULATIONS

The relationship between coagulation factor VII (FVII) levels in plasm a and FVII genotypes, determined by three polymorphisms (5'F7, IVS7, a nd 353R/Q), were studied in 500 control subjects enrolled in a Europea n multicenter study. The selection of particular FVII genotypes and th e analysis of variance clearly indicated the independent contribution of a single 5'F7 insertion (A2) or 353Q (M2) allele to lowering plasma levels of activated FVII (FVIIa) (by a mean 25%). The M2 allele alone was found to make a major contribution to the genetically determined component of the FVIIa levels. Genotypes associated with low FVII leve ls were significantly rarer in the northern part of Europe (Oslo) than in the southern part (Rome, Murcia). The contribution made by the FVI I genotype to the total variance of FVIIa levels was higher (30%) than that made to either FVII activity (25%) or FVII antigen (12%). Subjec ts with different FVII genotypes showed up to fivefold differences in mean FVIIa values, thus allowing attribution of a substantial part of the considerable interindividual variation to genetic variation, which may be of assistance in the interpretation of FVIIa levels on an indi vidual basis. When FVII levels were adjusted by age and by triglycerid e levels, the contribution of FVII genotypes to the FVII phenotypic va riance was virtually unchanged. Taken together, these data indicate th at in healthy control subjects the FVII genotype is a major predictor of plasma FVIIa levels and would support further study on the role of FVII genetic components in the development of cardiovascular disease.