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.
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.
Authors: Weihong Tang; Christine Schwienbacher; Lorna M Lopez; Yoav Ben-Shlomo; Tiphaine Oudot-Mellakh; Andrew D Johnson; Nilesh J Samani; Saonli Basu; Martin Gögele; Gail Davies; Gordon D O Lowe; David-Alexandre Tregouet; Adrian Tan; James S Pankow; Albert Tenesa; Daniel Levy; Claudia B Volpato; Ann Rumley; Alan J Gow; Cosetta Minelli; John W G Yarnell; David J Porteous; John M Starr; John Gallacher; Eric Boerwinkle; Peter M Visscher; Peter P Pramstaller; Mary Cushman; Valur Emilsson; Andrew S Plump; Nena Matijevic; Pierre-Emmanuel Morange; Ian J Deary; Andrew A Hicks; Aaron R Folsom Journal: Am J Hum Genet Date: 2012-06-14 Impact factor: 11.025
Authors: Lorna M Houlihan; Gail Davies; Albert Tenesa; Sarah E Harris; Michelle Luciano; Alan J Gow; Kevin A McGhee; David C Liewald; David J Porteous; John M Starr; Gordon D Lowe; Peter M Visscher; Ian J Deary Journal: Am J Hum Genet Date: 2010-03-18 Impact factor: 11.025
Authors: Weihong Tang; Martina Teichert; Daniel I Chasman; John A Heit; Pierre-Emmanuel Morange; Guo Li; Bruno H Ch Stricker; Paul M Ridker; Aaron R Folsom; Nicholas L Smith; Nathan Pankratz; Frank W Leebeek; Guillaume Paré; Mariza de Andrade; Christophe Tzourio; Bruce M Psaty; Saonli Basu; Rikje Ruiter; Lynda Rose; Sebastian M Armasu; Thomas Lumley; Susan R Heckbert; André G Uitterlinden; Mark Lathrop; Kenneth M Rice; Mary Cushman; Albert Hofman; Jean-Charles Lambert; Nicole L Glazer; James S Pankow; Jacqueline C Witteman; Philippe Amouyel; Joshua C Bis; Edwin G Bovill; Xiaoxiao Kong; Russell P Tracy; Eric Boerwinkle; Jerome I Rotter; David-Alexandre Trégouët; Daan W Loth Journal: Genet Epidemiol Date: 2013-05-05 Impact factor: 2.135
Authors: Laura B Harrington; Kerri L Wiggins; Colleen M Sitlani; Marc Blondon; Astrid van Hylckama Vlieg; Frits R Rosendaal; Susan R Heckbert; Bruce M Psaty; Nicholas L Smith Journal: Thromb Haemost Date: 2015-12-03 Impact factor: 5.249
Authors: Aaron R Folsom; Weihong Tang; Nicholas S Roetker; Susan R Heckbert; Mary Cushman; James S Pankow Journal: Am J Hematol Date: 2015-11 Impact factor: 10.047