Vitamin K epoxide reductase complex subunit 1 gene polymorphism is associated with atherothrombotic complication after drug-eluting stent implantation: 2-Center prospective cohort study

Am Heart J. 2009 May;157(5):908-12. doi: 10.1016/j.ahj.2009.02.001. Epub 2009 Mar 21.

Abstract

Background: Single nucleotide polymorphisms of vitamin K epoxide reductase complex subunit 1 (VKORC1) was reported to have association with arterial vascular disease. We investigated whether single nucleotide polymorphism of VKORC1 +2255 is associated with clinical outcomes among patients who underwent drug-eluting stent (DES) implantation.

Methods: We prospectively collected genomic DNA in patients who underwent DES deployment from September 2003 to December 2006 and compared clinical outcomes according to their VKORC1 genotype at the locus + 2255 (rs 2359612). The primary end point was composite of atherothrombotic events (cardiac death, myocardial infarction, and nonhemorrhagic stroke).

Results: Mean follow-up duration was 631 +/- 251 days. Genotyping was completed in 764 cases (TT genotype [n = 640, 83.8%] vs non-TT [CC or CT] genotype [n = 124, 16.2%]). Non-TT group showed more composite events than TT group (7.3% vs 3.0%, P = .032). In the Cox regression analysis, non-TT genotype of VKORC gene was a significant predictor of atherothrombotic events (hazard ratio 2.56, 95% confidence interval 1.14-5.78). In the event-free survival analysis, non-TT group also showed significantly poorer cardiovascular events-free survival rate than TT group (P = .02).

Conclusions: VKORC1 genotype is associated with cardiovascular events in patients with DES implantation, suggesting the role of coagulation system.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / complications
  • Atherosclerosis / enzymology
  • Atherosclerosis / genetics*
  • Coronary Disease / surgery
  • DNA / genetics*
  • Drug-Eluting Stents*
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Korea / epidemiology
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / blood
  • Mixed Function Oxygenases / genetics*
  • Myocardial Revascularization / adverse effects*
  • Myocardial Revascularization / instrumentation
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Postoperative Complications
  • Prospective Studies
  • Survival Rate
  • Thrombosis / enzymology
  • Thrombosis / etiology*
  • Thrombosis / mortality
  • Time Factors
  • Vitamin K Epoxide Reductases

Substances

  • DNA
  • Mixed Function Oxygenases
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases