A FEASIBILITY STUDY OF RISK STRATIFICATION FOR RECURRENT VENOUS THROMBOSIS BY MULTIPLE SNP ANALYSIS
Abstract number: P-W-495
van Hylckama Vlieg1 A., Rosendaal2 F.R., Bare3 L.A., Arellano3 A.R., Young3 B.A., Baglin4 T.P.
11Clinical Epidemiology 22Clinical Epidemiology/Thrombosis and Haemostasis Research Center, Leiden University Medical Center, Leiden, Netherlands 33Celera, Inc., Alameda, United States 44Haematology, Addenbrooke's Hospital, Cambridge, United Kingdom
How-to-cite van Hylckama Vlieg A, Rosendaal FR, Bare LA, Arellano AR, Young BA, Baglin TP. A FEASIBILITY STUDY OF RISK STRATIFICATION FOR RECURRENT VENOUS THROMBOSIS BY MULTIPLE SNP ANALYSIS. J Thromb Haemost 2007; 5 Supplement 2: P-W-495
Abstract
Introduction: Testing for individual single nucleotide polymorphisms (SNPs) has not been shown to predict risk of recurrent thrombosis. We conducted a proof-of-principle feasibility study to assess whether measurement of multiple SNPs might have clinical utility.
Methods: Samples from patients enrolled in the Leiden Thrombophilia Study (LETS) and the Cambridge venous thromboembolism (CVTE) study were combined (n=817). Both studies consisted of patients with a first objectively diagnosed deep venous thrombosis. Twenty-five SNPs, either established or putative risk factors for venous and arterial disease, were measured by Celera. Hazard ratios of recurrence were calculated for heterozygous and homozygous carriers combined using Cox regression analysis. All hazard ratios were adjusted for study, i.e., LETS or CVTE. SNPs were ranked according to individual hazard ratio for recurrence of deep venous thrombosis.
Results: None of the individual SNPs was strongly associated with the risk of recurrent venous thrombosis. The highest relative risk of recurrence was associated with the factor VII 10976G/A polymorphism and the factor V Leiden polymorphism with hazard ratios of 1.3 and 1.2, respectively. Increasing hazard ratios were found with addition of sequential SNPs added in rank order of hazard ratios from the single SNP analysis. Carriers of the first two (FVII, FVL), the first three (FVII, FVL, MTHFR), or the first four polymorphisms (FVII, FVL, MTHFR, FGB455) had a hazard ratio of 1.7, 2.7, and 5.4, respectively. However, with addition of each SNP the number of carriers rapidly reduced [number of carriers (with recurrences): F7 + FVL: 32 (7), F7 + FVL + MTHFR: 19 (6), F7 + FVL + MTHFR + FGB455: 3 (1)].
Conclusions: These results suggest that a combination of thrombosis associated SNPs predict recurrence risk while determination of individual SNPs does not. Since few individuals carry several variants, the determination of such SNPs and their combinations is too uncertain to be of clinical utility yet.
