title: Influence of proband's characteristics on the risk for venous thromboembolism in relatives with factor V Leiden or prothrombin G20210A polymorphisms.
abstract: In family studies, the risk for venous thromboembolism (VTE) in relatives with factor V Leiden (FVL) or G20210A prothrombin (PT20210A) gene polymorphisms may differ according to genotype and clinical presentation of the proband. To address this hypothesis, a retrospective cohort family study was carried out on 192 kindreds with at least one member with homozygous FVL or PT20210A, for a total of 886 relatives. The proband of the family was heterozygous in 68 and homozygous or with both polymorphisms in 124 kindreds. Twenty-three probands were asymptomatic, 11 had had arterial thrombosis, 7 obstetrical complications, and 151 venous thrombosis (122 VTE and 29 superficial vein thrombosis). The incidence of VTE (per 1000 patient-years) in relatives was higher when the proband had heterozygous rather than homozygous polymorphism (1.25 [95% confidence interval (CI), 0.73-1.91] vs 0.44 [0.19-0.78]) and when the proband had had VTE instead of other or no clinical manifestations (0.95 [0.57-1.42] vs 0.50 [0.19-0.96]). Compared with relatives belonging to kindreds with homozygous probands without VTE, the adjusted hazard ratio of VTE for relatives selected from kindreds with heterozygous probands with VTE was 4.14 (95% CI, 1.17-14.71). The genotype and clinical presentation of the proband influence the risk for VTE in relatives with FVL or PT20210A.
authors.affiliation: A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: Bucciarelli
authors.forename: Valerio
authors.initials: V
authors.lastname: De Stefano
authors.forename: Serena M
authors.initials: SM
authors.lastname: Passamonti
authors.forename: Daniela
authors.initials: D
authors.lastname: Tormene
authors.forename: Cristina
authors.initials: C
authors.lastname: Legnani
authors.forename: Elena
authors.initials: E
authors.lastname: Rossi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castaman
authors.forename: Paolo
authors.initials: P
authors.lastname: Simioni
authors.forename: Michela
authors.initials: M
authors.lastname: Cini
authors.forename: Ida
authors.initials: I
authors.lastname: Martinelli
mesh_terms: D000328:Adult; D018572:Disease-Free Survival; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011516:Prothrombin / Q000235:genetics*; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin