title: F11 is associated with recurrent VTE in women. A prospective cohort study.
abstract: Genetic associations for the reoccurrence of venous thromboembolism (VTE) are not well described. Our aim was to investigate if common genetic variants, previously found to contribute to the prediction of first time thrombosis in women, were associated with risk of recurrence. The Thromboembolism Hormone Study (TEHS) is a Swedish nationwide case-control study (2002-2009). A cohort of 1,010 women with first time VTE was followed up until a recurrent event, death or November 2011. The genetic variants in F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446 were assessed together with clinical variables. Recurrence rate was calculated as the number of events over the accumulated patient-time. Cumulative recurrence was calculated by Kaplan-Meier curve. Cox proportional-hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) between groups. A total of 101 recurrent events occurred during a mean follow-up time of five years. The overall recurrence rate was 20 per 1,000 person-years (95% CI; 16-24). The recurrence rate was highest in women with unprovoked first event and obesity. Carriers of the risk alleles of F5 rs6025 (HR=1.7 (95% CI; 1.1-2.6)) and F11 rs2289252 (HR=1.8 (95% CI; 1.1-3.0)) had significantly higher rates of recurrence compared to non-carriers. The cumulative recurrence was 2.5-fold larger in carriers of both F5 rs6025 and F11 rs2289252 than in non-carriers at five years follow-up. In conclusion, F5 rs6025 and F11 rs2289252 contributed to the risk of recurrent VTE and the combination is of potential clinical relevance for risk prediction.
authors.forename: Maria
authors.initials: M
authors.lastname: Bruzelius
authors.forename: Maria
authors.initials: M
authors.lastname: Ljungqvist
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.forename: Annica
authors.initials: A
authors.lastname: Bergendal
authors.forename: Rona J
authors.initials: RJ
authors.lastname: Strawbridge
authors.forename: Margareta
authors.initials: M
authors.lastname: Holmström
authors.forename: Angela
authors.initials: A
authors.lastname: Silveira
authors.forename: Helle
authors.initials: H
authors.lastname: Kieler
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.forename: Gerd
authors.initials: G
authors.lastname: Lärfars
authors.affiliation: Jacob Odeberg, MD PhD, Department of Proteomics, School of Biotechnology, Royal Institute of Technology (KTH), Science for Life Laboratory Stockholm, Box 1031, 171 21 Solna, Sweden, Tel: +46 70 2087571, Fax: +46 8 51775084, Email: jacob.odeberg@scilifelab.se.
authors.forename: Jacob
authors.initials: J
authors.lastname: Odeberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics* / Q000378:metabolism; D005172:Factor XI / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D013548:Sweden; D054556:Venous Thromboembolism / Q000097:blood* / Q000175:diagnosis / Q000235:genetics
chemical_list: D005165:Factor V; D005172:Factor XI
keywords: Epidemiology; polymorphism; recurrence; single nucleotide; venous thrombosis; women