Erratum in van 't Hooft et al. Two common functional polymorphisms in the promoter region of the coagulation factor VII gene determining plasma factor VII activity and mass concentration. Blood. 1999;93:3432-3441.

Recent studies have provided evidence for associations between common polymorphic markers in the coagulation factor VII (FVII) gene and plasma FVII levels. Here we describe two common, nonrelated, functional polymorphisms in the promoter region of the FVII gene, a G to T substitution at position −401 and a novel G to A substitution at position −402. Both polymorphisms strongly influence the binding properties of nuclear protein(s). The rare −401T allele is associated with a reduced basal rate of transcription of the FVII gene in human hepatoblastoma cells and with reduced plasma concentrations of total FVII (VIIag) and fully activated FVII molecules (VIIa). In contrast, the rare −402A allele confers increased transcriptional activity and is associated with increased plasma FVII levels. Together, the two polymorphisms explained 18% and 28% of the variation in VIIag and VIIa, respectively, in a group of 183 healthy, middle-aged men. It is concluded that these polymorphisms are important for the regulation of the plasma levels of FVII and that they are likely to be useful genetic markers to resolve the issue of whether a causal relationship exists between FVII levels and risk of coronary heart disease.

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Characterization of Transcriptional Regulatory Elements in the Promoter Region of the Murine Blood Coagulation Factor VII Gene

Journal of Biological Chemistry ◽

10.1074/jbc.273.4.2277 ◽

1998 ◽

Vol 273 (4) ◽

pp. 2277-2287 ◽

Cited By ~ 16

Author(s):

Daniel R. Stauffer ◽

Beatrice N. Chukwumezie ◽

Julie A. Wilberding ◽

Elliot D. Rosen ◽

Francis J. Castellino

Keyword(s):

Blood Coagulation ◽

Promoter Region ◽

Coagulation Factor ◽

Regulatory Elements ◽

Factor Vii ◽

Transcriptional Regulatory Elements ◽

Coagulation Factor Vii ◽

Transcriptional Regulatory

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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

Thrombosis and Haemostasis ◽

10.1160/th04-09-0616 ◽

2005 ◽

Vol 93 (02) ◽

pp. 351-358 ◽

Cited By ~ 14

Author(s):

Margita Eriksson-Berg ◽

Hiroyuki Deguchi ◽

Emma Hawe ◽

Daniela Scanavini ◽

Kristina Orth-Gomér ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Large Scale ◽

Plasma Concentrations ◽

Coagulation Factor ◽

Factor Vii ◽

Major Influence ◽

Serum Triglycerides ◽

Coagulation Factor Vii ◽

Functional Polymorphisms

SummaryPlasma 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.

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Oestrogenic repression of human coagulation factor VII expression mediated through an oestrogen response element sequence motif in the promoter region

Human Molecular Genetics ◽

10.1093/hmg/11.7.723 ◽

2002 ◽

Vol 11 (7) ◽

pp. 723-731 ◽

Cited By ~ 18

Author(s):

R. Di Bitondo

Keyword(s):

Promoter Region ◽

Coagulation Factor ◽

Factor Vii ◽

Sequence Motif ◽

Response Element ◽

Coagulation Factor Vii ◽

Human Coagulation Factor Vii ◽

Element Sequence

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The Decanucleotide Insertion/Deletion Polymorphism in the Promoter Region of the Coagulation Factor VII Gene and the Risk of Familial Myocardial Infarction

Thrombosis Research ◽

10.1016/s0049-3848(99)00220-0 ◽

2000 ◽

Vol 98 (1) ◽

pp. 9-17 ◽

Cited By ~ 27

Author(s):

Augusto Di Castelnuovo ◽

Andria D'Orazio ◽

Concetta Amore ◽

Anna Falanga ◽

Maria Benedetta Donati ◽

...

Keyword(s):

Myocardial Infarction ◽

Promoter Region ◽

Coagulation Factor ◽

Factor Vii ◽

Deletion Polymorphism ◽

Coagulation Factor Vii

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Genetic Effects for Plasma Factor VII Levels Independent of and in Common with Triglycerides

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614482 ◽

1999 ◽

Vol 81 (03) ◽

pp. 382-386 ◽

Cited By ~ 15

Author(s):

Nancy Pedersen ◽

Nils Egberg ◽

Ulf Faire ◽

Yuling Hong

Keyword(s):

Environmental Factors ◽

Genetic Factors ◽

Coagulation Factor ◽

Genetic Effects ◽

Factor Vii ◽

Genetic Influences ◽

Serum Triglycerides ◽

Coagulation Factor Vii ◽

Plasma Factor ◽

The Individual

Summary Background. Coagulation factor VII has been demonstrated as a potential risk factor for cardiovascular disease. Both genes and non-genetic factors are related to plasma levels of factor VII. However, the extent to which genetic effects influence variability in plasma factor VII levels is unknown. Further, increased levels of plasma factor VII are associated with serum triglycerides, yet the reason for this association is not fully understood. Methods and Results. Quantitative genetic analyses were applied to evaluate the relative importance of genetic and different environmental influences on plasma factor VII levels and to test the significance of genetic and environmental factors in common to factor VII and triglycerides in 215 pairs of middle-aged and elderly twins, of whom 104 were reared apart and 120 were women. Genetic influences were found to account for 57% of the individual differences in plasma factor VII levels, whereas shared-rearing and residual-familial environmental factors were not significant. Furthermore, a significant genetic correlation of 0.38 was found between factor VII and triglycerides, but the environmental correlation between these two measures was not significant. Genetic factors in common to factor VII and triglycerides explain about 7% of the total variance for factor VII. Conclusion. The present study suggests that there are substantial genetic influences on plasma factor VII levels. Furthermore, genetic effects explain the phenotypic association between factor VII and triglycerides.

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