Homozygosity in the single nucleotide polymorphism Ser128Arg in the E-selectin gene associated with recurrent venous thromboembolism

Arch Intern Med. 2006 Aug;166(15):1655-9. doi: 10.1001/archinte.166.15.1655.


Background: The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin gene is overrepresented 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: A total of 585 patients were prospectively observed after first VTE for recurrent, objectively documented, symptomatic VTE. Patients with secondary VTE, homozygous factor V Leiden, natural inhibitor deficiencies, lupus anticoagulant, or long-term anticoagulation therapy were excluded. The S128R SNP was genotyped by mutagenically separated polymerase chain reaction.

Results: A total of 102 patients (17%) were heterozygous, and 11 were homozygous (2%) for the Ser128Arg mutation. Ninety patients (15%) had recurrent VTE during follow-up. Homozygosity for the Ser128Arg SNP increased the cumulative likelihood, particularly for early recurrent VTE (log rank test, P<.05) and was an independent predictor of recurrent VTE (hazard ratio [HR], 4.1; 95% confidence interval [CI], 1.5-11.4) in a multivariate Cox regression model. In contrast, heterozygosity for the polymorphism was associated with an unaltered HR (HR, 1.1; 95% CI, 0.6-1.9) for recurrent VTE.

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

MeSH terms

  • Adult
  • Arginine
  • E-Selectin / genetics*
  • Female
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Recurrence
  • Serine
  • Thromboembolism / genetics*
  • Venous Thrombosis / genetics*


  • E-Selectin
  • Serine
  • Arginine