title: Influence of factor VII gene polymorphisms and environmental factors on plasma coagulation factor VII concentrations in middle-aged women with and without manifest coronary heart disease.
abstract: 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.
authors.affiliation: Cardiology Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Margita
authors.initials: M
authors.lastname: Eriksson-Berg
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Deguchi
authors.forename: Emma
authors.initials: E
authors.lastname: Hawe
authors.forename: Daniela
authors.initials: D
authors.lastname: Scanavini
authors.forename: Kristina
authors.initials: K
authors.lastname: Orth-Gomér
authors.forename: Karin
authors.initials: K
authors.lastname: Schenck-Gustafsson
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Angela
authors.initials: A
authors.lastname: Silveira
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
mesh_terms: D000704:Analysis of Variance; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005167:Factor VII / Q000032:analysis / Q000235:genetics*; D015942:Factor VIIa / Q000032:analysis / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D014280:Triglycerides; D005167:Factor VII; D015942:Factor VIIa