Genetic determinants of response to aspirin: appraisal of 4 candidate genes

Thromb Res. 2011 Jul;128(1):47-53. doi: 10.1016/j.thromres.2011.02.019. Epub 2011 Mar 22.

Abstract

Introduction: Intersubject variability in platelet response to aspirin could be related to genetic factors that regulate platelet enzymes or receptors. This study evaluates the impact of the selected polymorphisms in the COX-1 gene, the CYP5A1 gene, the P2RY1 receptor gene, and the GPIIbIIIa receptor gene on platelet response to aspirin and risk of suffering from major adverse cardiovascular and cerebrovascular events (MACCE).

Materials and methods: 192 Caucasian patients with stable coronary artery disease treated with daily aspirin were recruited and followed for 3 years. Platelet aggregation was measured by light transmission aggregometry with arachidonic acid (1.6 mM) and adenosine diphosphate (5, 10 or 20 μM) used as agonists. Genotyping was performed by standard PCR methods.

Results: Arachidonic acid-induced platelet aggregation was unaffected by the COX-1 22C/T and by the Pl(A1/A2) polymorphisms. However, carriers of the 1622 G/G genotype of the P2RY1 gene had significantly higher levels of arachidonic acid-induced platelet aggregation compared with non-carriers (AA 2.0%, AG 2.0% vs. GG 9.0%, p=0.047). Carrying the 1622 G/G genotype increased the risk of inadequate platelet response to aspirin, defined as arachidonic acid-induced aggregation ≥ 20%, by a factor of 8.5 (1.4 - 53.3, p=0.022) and the risk of 3-year MACCE by a factor of 7 (1.4 - 34.7, p=0.017).

Conclusion: The 1622A/G mutation of the P2RY1 gene could contribute to inadequate platelet response to aspirin and is associated with an increased risk of suffering from MACCE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / pharmacology*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / genetics
  • Cyclooxygenase 1 / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Male
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation / genetics*
  • Platelet Glycoprotein GPIIb-IIIa Complex / genetics
  • Polymorphism, Genetic
  • Prospective Studies
  • Receptors, Purinergic P2Y1 / genetics
  • Thromboxane-A Synthase / genetics

Substances

  • P2RY1 protein, human
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, Purinergic P2Y1
  • Cyclooxygenase 1
  • Thromboxane-A Synthase
  • Aspirin