The association of four common polymorphisms from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity: a meta-analysis

PLoS One. 2013 Nov 14;8(11):e78093. doi: 10.1371/journal.pone.0078093. eCollection 2013.

Abstract

Objective: Evidence is mounting suggesting that a strong genetic component underlies aspirin insensitivity. To generate more information, we aimed to evaluate the association of four common polymorphisms (rs3842787, rs20417, rs201184269, rs1126643) from four candidate genes (COX-1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity via a meta-analysis.

Methods and results: In total, there were 4 (353/595), 6 (344/698), 10 (588/878) and 7 (209/676) articles (patients/controls) qualified for rs3842787, rs20417, rs20118426 and rs1126643, respectively. The data were extracted in duplicate and analyzed by STATA software (Version 11.2). The risk estimate was expressed as odds ratio (OR) and 95% confidence interval (95% CI). Analyses of the full data set indicated significant associations of rs20417 (OR; 95% CI; P: 1.86; 1.44-2.41; <0.0005) and rs1126643 (2.37; 1.44-3.89; 0.001) with aspirin insensitivity under allelic model. In subgroup analyses, the risk estimate for rs1126643 was greatly potentiated among patients with aspirin semi-resistance relative to those with aspirin resistance, especially under dominant model (aspirin semi-resistance: 5.44; 1.42-20.83; 0.013 versus aspirin resistance: 1.96; 1.07-3.6; 0.03). Further grouping articles by ethnicity observed a stronger prediction of all, but rs20417, examined polymorphisms for aspirin insensitivity in Chinese than in Caucasians. Finally, meta-regression analyses observed that the differences in percentage of coronary artery disease (P = 0.034) and averaged platelet numbers (P = 0.012) between two groups explained a large part of heterogeneity for rs20417 and rs1126643, respectively.

Conclusion: Our findings provide strong evidence that COX-2 and ITGA2 genetic defects might increase the risk of having aspirin insensitivity, especially for aspirin semi-resistance and in Chinese populations.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Asian People
  • Aspirin / adverse effects*
  • Cyclooxygenase 1 / genetics*
  • Cyclooxygenase 2 / genetics*
  • Humans
  • Integrin alpha2 / genetics*
  • Platelet Count
  • Polymorphism, Genetic*
  • Risk Factors
  • White People

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • ITGA2B protein, human
  • Integrin alpha2
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Aspirin

Grants and funding

This work was supported by the Shanghai Rising Star Program (11QA1405500). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.