ABCB1 C3435T polymorphism and response to clopidogrel treatment in coronary artery disease (CAD) patients: a meta-analysis

PLoS One. 2012;7(10):e46366. doi: 10.1371/journal.pone.0046366. Epub 2012 Oct 9.

Abstract

Background: A number of investigators have evaluated the association between the ABCB1 polymorphism and clopidogrel responding, but the results have been inconclusive. To examine the risk of high platelet activity and poor clinical outcomes associated with the ABCB1 C3435T polymorphism in CAD patients on clopidogrel, all available studies were included in the present meta-analysis.

Methods: We performed a systematic search of PubMed, Scopus and the Cochrane library database for eligible studies. Articles meeting the inclusion criteria were comprehensively reviewed, and the available data were accumulated by the meta-analysis.

Results: It was demonstrated that the ABCB1 C3435T variation was associated with the risk of early major adverse cardiovascular events (MACE) (T vs. C OR, 1.34; 95% CI, 1.10 to 1.62; P=0.003; TT vs. CC: OR, 1.77; 95% CI, 1.19 to 2.63; P=0.005; CT + TT vs.CC: OR, 1.48; 95% CI, 1.06 to 2.06; P=0.02) and the polymorphism was also associated with the risk of the long-term MACE in patients on clopidogrel LD 300 mg (T vs. C: OR, 1.28; 95% CI, 1.10 to 1.48; P=0.001; TT vs. CC: OR, 1.59; 95% CI, 1.19 to 2.13; P=0.002; CT + TT vs.CC: OR, 1.39; 95% CI, 1.08 to 1.79; P=0.01). The comparison of TT vs. CC was associated with a reduction in the outcome of bleeding (TT vs. CC: OR, 0.51; 95% CI, 0.40 to 0.66; P<0.00001). However, the association between ABCB1 C3435T polymorphism and platelet activity and other risk of poor clinical outcomes was not significant.

Conclusions: The evidence from our meta-analysis indicated that the ABCB1 C3435T polymorphism might be a risk factor for the MACE in patients on clopidogrel LD 300 mg, and that TT homozygotes decreased the outcome of bleeding compared with CC homozygotes.

Publication types

  • Meta-Analysis

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Clopidogrel
  • Coronary Artery Disease / drug therapy*
  • Humans
  • Platelet Aggregation Inhibitors
  • Polymorphism, Genetic*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine

Grants and funding

The authors have no support or funding to report.