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  • Title: Genetic variants associated with deep vein thrombosis: the F11 locus.
    Author: Li Y, Bezemer ID, Rowland CM, Tong CH, Arellano AR, Catanese JJ, Devlin JJ, Reitsma PH, Bare LA, Rosendaal FR.
    Journal: J Thromb Haemost; 2009 Nov; 7(11):1802-8. PubMed ID: 19583818.
    Abstract:
    BACKGROUND: Recent studies have found associations between deep vein thrombosis (DVT) and single nucleotide polymorphisms (SNPs) in a 4q35.2 locus that contains genes encoding factor XI (F11), a cytochrome P450 family member (CYP4V2), and prekallikrein (KLKB1). OBJECTIVE: We investigated which of the common SNPs in this locus are independently associated with DVT. METHODS: The study populations were the Leiden Thrombophilia Study (LETS) (443 DVT cases and 453 controls) and the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study) (2712 DVT cases and 4634 controls). We assessed the association between DVT and 103 SNPs in a 200 kb region using logistic regression. RESULTS: We found that two SNPs (rs2289252 and rs2036914 in F11) were independently associated with DVT. After adjusting for age, sex, and the other SNP, the odds ratios (risk vs. non-risk homozygotes) of these two SNPs were 1.49 for rs2289252 (95% CI, 1.25-1.76) and 1.33 for rs2036914 (95% CI, 1.11-1.59). We found that rs2289252 was also associated with FXI levels, as has been previously reported for rs2036914; these two SNPs remained associated with DVT with somewhat attenuated risk estimates after adjustment for FXI levels. CONCLUSION: Two SNPs, rs2289252 and rs2036914 in F11, appear to independently contribute to the risk of DVT, a contribution that is explained at least in part by an association with FXI levels.
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