title: Asymptomatic carriership of factor V Leiden and genotypes of the fibrinogen gene cluster.
abstract: We investigated the role of frequent fibrinogen polymorphisms in venous thromboembolic disease in conjunction with inherited thrombophilia. Two hundred unrelated subjects, all carriers of the factor V R506Q mutation (FV Leiden), were genotyped at the fibrinogen gene cluster. Among these subjects, 100 had experienced previous venous thromboembolism (VTE) and 100 were still asymptomatic for VTE. Significant differences were observed between the groups for the BclI polymorphism (P = 0.004). Scanning, by sequencing the DNA regions flanking the BclI marker, revealed new polymorphisms, a C to T transition and a G to T transversion at 1520 and 3369 base pairs 3' to the beta gene stop codon respectively. These markers showed less association with the clinical phenotype than BclI itself. A combined genotype including 10 markers was more frequent among the asymptomatic subjects (17%) than among patients (3%), and was associated with a reduction in fibrinogen antigen level (2.42 +/- 0.35 vs 2.69 +/- 0.41 g/l, P = 0.028) among the asymptomatic subjects. Our data suggest that, in the presence of inherited thrombophilia, frequent fibrinogen polymorphisms may interact to modulate the risk of venous thromboembolism.
authors.affiliation: Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Unità di Ricerca Clinica sulla Trombofilia 'Marino Golinelli', Divisione di Angiologia, Azienda Ospedaliera di Bologna, Policlinico S.Orsola-Malpighi, Bologna, Italia.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Marchetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferraresi
authors.forename: Cristina
authors.initials: C
authors.lastname: Legnani
authors.forename: Mirko
authors.initials: M
authors.lastname: Pinotti
authors.forename: Barbara
authors.initials: B
authors.lastname: Lunghi
authors.forename: Chiara
authors.initials: C
authors.lastname: Scapoli
authors.forename: Donato
authors.initials: D
authors.lastname: Gemmati
authors.forename: Sergio
authors.initials: S
authors.lastname: Coccheri
authors.forename: Gualtiero
authors.initials: G
authors.lastname: Palareti
authors.forename: Francesco
authors.initials: F
authors.lastname: Bernardi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004247:DNA / Q000032:analysis / Q000235:genetics; D005165:Factor V / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D019851:Thrombophilia / Q000235:genetics; D020246:Venous Thrombosis / Q000235:genetics
chemical_list: C095381:factor V Leiden; D005165:Factor V; D005340:Fibrinogen; D004247:DNA