Influence of factor VII gene polymorphisms and environmental factors on plasma coagulation factor VII concentrations in middleaged women with and without manifest coronary heart disease

Margita Eriksson-Berg; Hiroyuki Deguchi; Emma Hawe; Daniela Scanavini; Kristina Orth-Gomér; Karin Schenck-Gustafsson; Steve E. Humphries; Angela Silveira; Anders Hamsten

doi:10.1160/TH04-09-0616

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(02): 351-358
DOI: 10.1160/TH04-09-0616

Cell Signalling and Vessel Remodelling

Schattauer GmbH

Influence of factor VII gene polymorphisms and environmental factors on plasma coagulation factor VII concentrations in middleaged women with and without manifest coronary heart disease

Margita Eriksson-Berg

¹Cardiology Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

,

Hiroyuki Deguchi

²Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

,

Emma Hawe

⁴Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College London Medical School, London, UK

,

Daniela Scanavini

²Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

,

Kristina Orth-Gomér

³Department of Public Health Sciences, Division of Preventive Medicine, Karolinska Institute, Stockholm, Sweden

,

Karin Schenck-Gustafsson

¹Cardiology Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

,

Steve E. Humphries

⁴Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Rayne Building, Royal Free and University College London Medical School, London, UK

,

Angela Silveira

²Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

,

Anders Hamsten

¹Cardiology Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

²Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

› Author Affiliations

Abstract

Summary

Plasma concentrations of coagulation factorVII (FVII) are determined by environmental and genetic factors. The influence of functional polymorphisms in the FVII gene (-670A>C, –402G>A, –401G>T and R353Q) and of established cardiovascular risk factors on plasma concentrations of FVII were investigated in a representative sample of middle-aged women with (n=238) and without (n=220) coronary heart disease (CHD). Specific and sensitive assays were used to measure FVII antigen (VIIag) and activated factorVII (VIIa).The effect of genotypes was markedly stronger on VIIa than on VIIag, with the percentage variation in FVII levels accounted for by genotypes being greater in controls than in patients. Of the four polymorphisms examined, only the R353Q contributed to the variation inVIIa (24.1% in patients and 30.3% in controls). The –401G>T and –670A>C promoter polymorphisms together accounted for 12.2% of the variation in VIIag amongst patients whereas the –401G>T polymorphism alone contributed 19.7% of the variation in VIIag in controls. Serum triglycerides exerted a major influence onVIIag in both patients (13.0%) and controls (7.2%).Three main haplotypes emerged from the four polymorphisms which accounted for 98% of all haplotypes. Large-scale prospective studies of CHD including FVII haplotypes and sensitive and specific FVII measurements are needed in women.

Keywords

Coagulation - factor VII - myocardial infarction - genetics

Full Text

References

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