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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2024-2028.)
© 1999 American Heart Association, Inc.

Thrombosis

Oral Contraceptives Highlight the Genotype-Specific Association Between Serum Phospholipids and Activated Factor VII

G. Mariani; J. Conard; F. Bernardi; R. Bertina; V. Vicente Garcia; H. Prydz; M. Samama; P. M. Sandset; M. Puopolo; M. V. Ciarla; R. Poso; G. D. Di Nucci; F. Ceci; G. Marchetti; for the European Union Concerted Action "Clotart"

From the Hematology and Bone Marrow Transplantation Unit (G.M.), University Hospital, Palermo; the Department of Human Biopathology (G.D.D.N., M.V.C., F.C.), University of Rome "La Sapienza," Rome; and the Department of Biochemistry and Molecular Biology (F.B., G.M.), University of Ferrara, Ferrara, Italy; Leiden University Medical Center (R.B.), Leiden, the Netherlands; the Department of Hematology (V.V.G., R.P), Murcia University Hospital, Murcia, Spain; the Biotechnology Centre (H.P.), University of Oslo, Oslo, Norway; Hotel Dieu Hospital (M.S., J.C.), Paris, France; Ulleval University Hospital (P.M.S.), Oslo, Norway; and the National Health Institute (M.P.), Rome, Italy.

Correspondence to Prof G. Mariani, Hematology and Bone Marrow Transplantation Unit, Palermo University Hospital, Via del Vespro, 129, 90127 Palermo, Italy. E-mail mariangu{at}tin.it

Abstract—The present analysis was undertaken to study the effect of oral contraceptive (OC) use on activated factor VII (FVIIa) in subjects characterized by FVII genotypes, with the further aim of evaluating the role of lipids in this pharmacological interaction. In OC users (n=42) and nonusers (n=130) of comparable age, we examined the FVII phenotypic variables (FVII coagulant activity [FVIIc], FVII antigen, and FVIIa), FVII genotypes (the 353R/Q and 5'F7 polymorphisms analyzed in combination; alleles M1/M2 and A1/A2, respectively), and a number of lipid and lipoprotein parameters: serum concentrations of total cholesterol (chol), low density lipoprotein and high density lipoprotein-chol, triglycerides, phospholipids (PhLs), apolipoprotein A1, and lipoprotein(a). PhLs, triglycerides, apolipoprotein A1, chol, FVII antigen, FVIIc, and high density lipoprotein-chol levels were shown to be statistically higher in users than nonusers. FVII levels, particularly those of FVIIa and FVIIc, were much higher in homozygotes for the A1 and M1 alleles (A11 M11), especially in OC users. A strong association was found between PhL and FVIIa: in the multiple regression analysis, women taking OCs who had elevated PhL concentrations also had very high levels of FVIIa, but only if their genotype was A11 M11. These results indicate that the increased FVII levels in OC users depend on the FVII genotype and that high PhL concentrations predict very high levels of FVIIa and FVIIc.

Key Words: factor VII • activated factor VII • phospholipids • factor VII genotype

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