© 1997 American Heart Association, Inc.
Articles |
Contribution of Factor VII Genotype to Activated FVII Levels
Differences in Genotype Frequencies Between Northern and Southern European Populations
From Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Ferrara, Italy (F.B., M.P.); Dipartimento di Biotecnologie Cellulari ed Ematologia, Università "La Sapienza," Rome, Italy (P.A., R.S.); Haemostasis and Thrombosis Research Centre, Leiden University Hospital, Leiden, The Netherlands (R.M.B.); Istituto Superiore di Sanità, Rome, Italy (F.C.); Haematology Unit, Hospital General Universitario, University of Murcia, Murcia, Spain (J.C., V.V.G.); Biotechnology Centre, University of Oslo, Oslo, Norway (H.P.); Laboratoire Central d'Hematologie, Hotel Dieu Laboratoire de Thrombose Experimental, Facultè Broissais Hotel Dieu, Paris, France (M.S.); Haematology Laboratory, Medical Clinic, Ullevaal Hospital, University of Oslo, Oslo, Norway (P.M.S.); and Cattedra di Ematologia, Università di Palermo, Italy (G.M.).
Correspondence to Prof Bernardi Francesco, Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Ferrara, Via Luigi Borsari 46, 44100 Ferrara, Italy. E-mail Ber{at}dns.unife.it
Abstract The relationship between coagulation factor VII (FVII) levels in plasma and FVII genotypes, determined by three polymorphisms (5'F7, IVS7, and 353R/Q), were studied in 500 control subjects enrolled in a European multicenter study. The selection of particular FVII genotypes and the 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 levels were significantly rarer in the northern part of Europe (Oslo) than in the southern part (Rome, Murcia). The contribution made by the FVII genotype to the total variance of FVIIa levels was higher (30%) than that made to either FVII activity (25%) or FVII antigen (12%). Subjects 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 individual basis. When FVII levels were adjusted by age and by triglyceride levels, the contribution of FVII genotypes to the FVII phenotypic variance was virtually unchanged. Taken together, these data indicate that 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.
Key Words: factor VIIa • factor VII genotype • multicenter study
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