Platelet gene polymorphisms and risk of bleeding in patients undergoing elective coronary angiography: A genetic substudy of the PRAGUE-8 trial

Abstract

Aim Utilization of cardiac catheterization has increased dramatically over time. Bleeding is a major prognostic predictor after percutaneous coronary catheterization procedures. This study aimed to assess the impact of eight polymorphisms of genes encoding platelet receptors and enzymes on the risk of bleeding in patients undergoing elective coronary angiography (CAG). Methods Polymorphisms of platelet receptors, GP Ia (807C>T, rs1126643), GP VI (13254T>C, rs1613662), GP IIIa (HPA-1, rs5918), PAR-1 (IVS-14A>T, rs168753), P2Y 12 (34C>T, rs6785930 and H1/H2 haplotype, rs2046934), and genetic variations of the gene coding for cyclooxygenase-1 (COX-1) (−842A>G, rs10306114 and 50C>T, rs3842787) were studied. The frequencies of gene polymorphisms carriers were investigated in 696 patients undergoing elective CAG because of suspected or proven stable coronary artery disease. Genotyping was done using PCR, followed by melting curve analysis with specific fluorescent hybridization probes. Results In patients undergoing elective CAG (without ad hoc percutaneous coronary intervention (PCI) and without clopidogrel pretreatment) a significant association was found between bleeding risk and variations in the gene coding for COX-1 (−842A>G and 50C>T) (both p = 0.013). Six other investigated polymorphisms did not show any influence on bleeding complications. After controlling for potential bleeding confounders, the association between COX-1 gene polymorphisms (−842A>G and 50C>T) and bleeding risk remained statistically significant (both odds ratios 12.1, p = 0.012). Conclusion Cyclooxygenase-1 −842G and 50T alleles significantly contribute to the risk of bleeding complications in patients undergoing elective CAG. Genetic testing is able to influence the safety of diagnostic cardiac catheterization in large numbers of low risk patients with borderline indications.