title: Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (factor V Leiden).
abstract: With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort study was performed in 810 family members identified through 174 probands who suffered from at least 1 episode of deep vein thrombosis and/or pulmonary embolism and had an inherited defect associated with thrombophilia (antithrombin, protein C, or protein S deficiency; factor V R506Q or prothrombin G20210A). Fifty-eight percent (468/810) of the family members had an inherited defect and 10% (47/468) were symptomatic. The HR2 haplotype was found in association with factor V R506Q more frequently in family members with venous thromboembolism (18%) than in those without (8%). Double heterozygosity for factor V R506Q and HR2 conferred a 3- to 4-fold increase in the relative risk of venous thromboembolism compared with factor V R506Q alone. The median age at first event was lower when the 2 defects were associated (46 v 52 years). No increase in risk of venous thromboembolism could be demonstrated when the HR2 haplotype was associated with inherited thrombophilic defects other than factor V R506Q. Because both factor V R506Q and the HR2 haplotype are very frequent, the effect of their coinheritance on the risk of venous thromboembolism might represent a clinically relevant issue, and screening for HR2 in carriers of factor V R506Q should be considered.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Department of Internal Medicine, IRCCS Maggiore Hospital and University of Milano, Milan, Italy. elena.faioni@unimi.it
authors.forename: E M
authors.initials: EM
authors.lastname: Faioni
authors.forename: F
authors.initials: F
authors.lastname: Franchi
authors.forename: P
authors.initials: P
authors.lastname: Bucciarelli
authors.forename: M
authors.initials: M
authors.lastname: Margaglione
authors.forename: V
authors.initials: V
authors.lastname: De Stefano
authors.forename: G
authors.initials: G
authors.lastname: Castaman
authors.forename: G
authors.initials: G
authors.lastname: Finazzi
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005165:Factor V / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D012306:Risk; D020246:Venous Thrombosis / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V