Homozygosity in the Single Nucleotide Polymorphism Ser128Arg in the E-Selectin Gene Is Associated with Recurrent Venous Thromboembolism.

Objective: The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin gene is over-represented in certain patient populations with atherosclerosis or restenosis. As this SNP enhances tissue factor triggered coagulation in humans during systemic inflammation, we hypothesized that it may also predispose for the development of recurrent venous thromboembolism (VTE).

Methods and Results: Patients (n=585) after first VTE were prospectively followed up for recurrent, objectively documented, symptomatic VTE. Patients with secondary VTE, homozygous Factor V Leiden, natural inhibitor deficiencies, lupus anticoagulant, or long term anticoagulation were excluded. The S128R SNP was genotyped by mutagenically separated PCR. One-hundred and two patients (17.4%) were heterozygous and 11 were homozygous (1.9%) for the Ser128Arg mutation. Ninety patients (15.4%) suffered from recurrent VTE during follow-up. Homozygosity for the Ser128Arg SNP increased the cumulative likelihood particularly for early recurrent VTE (log rank test p<0.05) and was an independent predictor of recurrent VTE (hazard ratio: 4.1; 95% CI 1.5–11.4) in a multivariate Cox Regression model. In contrast, heterozygosity for the polymorphism was associated with an unaltered hazard ratio (HR: 1.1; 95% CI 0.6–1.9) for recurrent VTE.

Conclusion: Homozygosity for the S128R E-selectin allele appears to increase the risk for recurrent VTE several-fold, and -if confirmed- may represent a novel risk factor for recurrent VTE. These results also expand our knowledge on the association of this SNP with thrombotic disorders.