Genetic variants of F11, statin use and venous thrombosis

Abstract

The F11 gene encodes factor (F)XI, a component of the intrinsic coagulation pathway. Single nucleotide polymorphisms (SNPs) in the F11 gene and high FXI antigen levels are associated with venous thrombosis (VT) [1,2]. Two F11 variants were found to be associated with VT in a recent fine mapping study conducted in the Leiden Thrombophilia Study and in the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study: rs2289252 (22771 T/C) in intron 12 and rs2036914 (7872 C/T) in intron 2 [3]. Carriers of two risk alleles, compared with those who carried no risk alleles, had odds ratios (OR) for VT of 1.84 [95% confidence interval (CI), 1.62–2.10] for rs2289252 and 1.84 (95% CI, 1.61–2.10) for rs2036914, and for carriers of one risk allele the OR was 1.41 (95% CI, 1.27–1.57) for rs2289252 and 1.42 (95% CI, 1.26– 1.61) for rs2036914 [3]. Although these two F11 SNPs were associated with FXI levels, they remained associated with VT after adjustment for FXI levels [3]. Several studies have shown that users of statins (a class of lipid-lowering HMG-CoA reductase inhibitors) have approximately 50% fewer VT events than non-users have [4–7]. In the MEGA study, we asked whether carriers of the rs2289252 and rs2036914 risk alleles, compared with non-carriers, were at an increased risk for VT among statin users and also among nonusers. The MEGA study recruited consecutive patients aged 18– 70 years with a first diagnosis of VT (deep vein thrombosis of