Genetic Modulation of Coagulation Factor VII Plasma Levels: Contribution of Different Polymorphisms and Gender-related Effects

Augusto Di Castelnuovo; Andria D’Orazio; Concetta Amore; Anna Falanga; Cornelis Kluft; Maria Benedetta Donati; Licia Iacoviello

doi:10.1055/s-0037-1615427

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1998; 80(04): 592-597
DOI: 10.1055/s-0037-1615427

Rapid Communication

Schattauer GmbH

Genetic Modulation of Coagulation Factor VII Plasma Levels: Contribution of Different Polymorphisms and Gender-related Effects

Augusto Di Castelnuovo

¹From the Istituto di Ricerche Farmacologiche Mario Negri, Unit of Genetics of Vascular Risk Factors, “Angela Valenti” Laboratory of Thrombosis Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy

,

Andria D’Orazio

¹From the Istituto di Ricerche Farmacologiche Mario Negri, Unit of Genetics of Vascular Risk Factors, “Angela Valenti” Laboratory of Thrombosis Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy

,

Concetta Amore

¹From the Istituto di Ricerche Farmacologiche Mario Negri, Unit of Genetics of Vascular Risk Factors, “Angela Valenti” Laboratory of Thrombosis Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy

,

Anna Falanga

²From the Hematology Department of Ospedali Riuniti di Bergamo, Bergamo, Italy

,

Cornelis Kluft

³From the Gaubius Laboratory, Leiden, The Netherlands

,

Maria Benedetta Donati

¹From the Istituto di Ricerche Farmacologiche Mario Negri, Unit of Genetics of Vascular Risk Factors, “Angela Valenti” Laboratory of Thrombosis Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy

,

Licia Iacoviello

¹From the Istituto di Ricerche Farmacologiche Mario Negri, Unit of Genetics of Vascular Risk Factors, “Angela Valenti” Laboratory of Thrombosis Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy

³From the Gaubius Laboratory, Leiden, The Netherlands

› Institutsangaben

Abstract

Summary

We studied the relationships among different polymorphisms of FVII gene in determining FVII levels, in a sample of 335 male and female Italian volunteers. The hypervariable region 4 (HVR4), the promoter decanucleotide insertion (-323 0/10 bp) and the R353Q polymorphisms of FVII gene were evaluated.

The association of HVR4 or -323 0/10 bp polymorphism with plasma FVII levels differed between gender (Interaction term: p = 0.02 and p = 0.03, respectively), showing stronger effect in males than in females. In males, the R353Q and the HVR4 polymorphisms showed an incremental influence on FVII variance (F = 8.9, p < 0.001 and F = 4.4, p = 0.01, respectively). Moreover, the effects of Q and 10 bp alleles on the reduction of FVII activity levels were significantly potentiated by the presence of H7 allele of HVR4 (Interaction term p = 0.03 for R353Q*HVR4 and p = 0.03 for -323 0/10 bp*HVR4). In conclusion, the effect of FVII polymorphisms on FVII levels was gender dependent and derived from a complex interaction among them. The HVR4 polymorphism seems to add an independent, albeit small, contribution to the regulation of FVII plasma levels.

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Referenzen

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