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Proof of principle of potential clinical utility of multiple SNP analysis for prediction of recurrent venous thrombosis

Summary.  Background: Individual single nucleotide polymorphisms (SNPs) associated with an increased risk of a first venous thrombosis do not predict risk of recurrent thrombosis. Objective: To assess the risk of recurrent venous thrombosis associated with multiple SNPs. Patients/methods: Fifteen nucleotide polymorphisms (SNPs), either established or putative risk factors for venous thrombosis, were measured in 817 unselected patients presenting with a first episode of venous thrombosis. Data from patients enrolled in the Leiden Thrombophilia Study (LETS) (n = 443) and the first Cambridge Prospective Cohort Study (n = 374) were combined. Hazard ratios for recurrence of thrombosis were calculated for individual SNPs. Results: Of the total study population, 117 patients had a recurrent event after a mean follow‐up of 4.6 years. The overall incidence rate was 30.8/1000 person years, corresponding with an annual risk of 3.1%. None of the individual SNPs was more than weakly associated with the risk of recurrent venous thrombosis. With addition of sequential SNPs, added in rank order of risk, the hazard ratios for recurrence increased by 1.7‐fold for carriers (3.8% of all patients) of the first two SNPs, 2.7‐fold for carriers of three (2.3%) and 5.1‐fold for carriers of four (0.4%). With addition of each SNP the number of carriers rapidly reduced. Conclusions: Although there is a substantially increased risk of recurrent thrombosis for carriers of several genetic variants, the clinical utility of multiple SNP analysis at present would be limited to a small proportion of patients.