Cytochrome P450 2C19 Polymorphism Is Associated With Poor Clinical Outcomes in Coronary Artery Disease Patients Treated With Clopidogrel

Mol Biol Rep. 2011 Mar;38(3):1697-702. doi: 10.1007/s11033-010-0282-0. Epub 2010 Sep 16.

Abstract

Patients with lesser degrees of platelet inhibition in response to clopidogrel appear to be at increased risk for recurrent ischemic events. Cytochrome P450 (CYP) polymorphisms have been proposed as possible mechanisms for nonresponsiveness to clopidogrel. Published data on the association between CYP2C19*2 polymorphism and atherothrombotic events are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of eight prospective cohort studies including 2,345 patients carrying CYP2C19*2 variant allele and 5,935 cases with the wild-type genotype were included in this meta-analysis. Overall, borderline statistically significantly elevated risk of adverse clinical events was associated with genotyping 681G>A polymorphism (for AA + GA vs. GG: OR, 1.46; 95% CI, 1.01 to 2.13; P = 0.05). The summary odds ratio showed a significant association between the CYP2C19*2 polymorphism and an increased risk of cardiac mortality in the follow-up period (OR, 2.07; 95% CI, 1.22 to 3.52; P = 0.007). When studies evaluating myocardial infarction, stent thrombosis, and ischemic stroke, the presence of the variant allele was associated with significantly increased risks of recurrent atherothrombotic events. In summary, this meta-analysis indicated that CYP2C19*2 carrier status is significantly associated with an increased risk of adverse cardiovascular events.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Clopidogrel
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / enzymology
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / mortality
  • Cytochrome P-450 CYP2C19
  • Humans
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / genetics
  • Myocardial Ischemia / drug therapy
  • Myocardial Ischemia / enzymology
  • Myocardial Ischemia / genetics
  • Odds Ratio
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Polymorphism, Single Nucleotide / genetics*
  • Stents / adverse effects
  • Stroke / drug therapy
  • Stroke / enzymology
  • Stroke / genetics
  • Thrombosis / drug therapy
  • Thrombosis / enzymology
  • Thrombosis / genetics
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine