The Prognostic Value of Combinations of Genetic Polymorphisms in the ITGB3, ITGA2, and CYP2C19*2 Genes in Predicting Cardiovascular Outcomes After Coronary Bypass Grafting

Genet Test Mol Biomarkers. 2018 Apr;22(4):259-265. doi: 10.1089/gtmb.2017.0177. Epub 2018 Feb 20.

Abstract

Aim: To determine if there are any associations between the single nucleotide polymorphisms (SNPs): rs2046934, rs1126643, rs5918, rs6065, rs4244285; rs4986893 and the occurrence of cardiovascular events (CVE) in patients following coronary artery bypass grafting (CABG) surgery.

Materials and methods: The study included 130 CABG patients with stable angina grades II-IV. After CABG 69 of the patients were treated with acetylsalicylic acid (ASA) alone, and 61 received dual antiplatelet therapy (ASA+clopidogrel). Platelet function was assessed by light transmission aggregometry with adenosinediphosphate and arachidonic acid. The SNPs were identified by real-time polymerase chain reaction (PCR) with electrophoretic detection. The mean follow-up period was equal to 10.9 ± 5.2 months. The primary end point included the composite of all-cause mortality, myocardial infarction (MI), and ischemic stroke.

Results: During the follow-up period 12 CVE were registered: 3 deaths, 6 MI, 3 strokes. Patients with composite mutant alleles of ITGB3+CYP2C19*2 or CYP2C19*2 + ITGA2, and with the mutant allele (*2) of CYP2C19, met end points more often than patients with other gene combinations (wild-type homozygotes, presence of one mutant allele of ITGB3 or ITGA2, the composite of mutant alleles of ITGB3+ITGA2 or ITGB3+ITGA2+CYP2C19*2; hazard ratio = 4, 95% confidence interval: 2.19-7.29, p = 0.008).

Conclusion: Carriage of a combination of mutant alleles in multiple genes including ITGB3+CYP2C19*2 or CYP2C19*2 + ITGA2 or CYP2C19*2 are possible predictors of CVE in patients after CABG.

Keywords: artery bypass surgery; cardiovascular events; genetic predictors.

MeSH terms

  • Aged
  • Alleles
  • Angina Pectoris / drug therapy
  • Angina Pectoris / surgery*
  • Aspirin / administration & dosage
  • Aspirin / therapeutic use
  • Clopidogrel
  • Combined Modality Therapy
  • Coronary Artery Bypass* / adverse effects
  • Cytochrome P-450 CYP2C19 / genetics*
  • Humans
  • Integrin alpha2 / genetics*
  • Integrin beta3 / genetics*
  • Middle Aged
  • Mutation
  • Platelet Aggregation
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • ITGB3 protein, human
  • Integrin alpha2
  • Integrin beta3
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine
  • Aspirin