The Frequency of the Minor Polymorphisms in the CYP2C19, VEGFR-2 Genes, and Clinical Outcomes in Russian and Buryat Patients with Acute Coronary Syndrome

Genet Test Mol Biomarkers. 2020 Jun;24(6):338-342. doi: 10.1089/gtmb.2019.0216. Epub 2020 May 11.

Abstract

Aim: To determine the differences in the frequencies of polymorphic variants at the rs4244285(*2), rs4986893 (*3), rs12248560 (*17), loci of the CYP2C19 gene, and the rs2305948 locus of the VEGFR-2 gene in patients receiving clopidogrel treatment as part of a 30-day clinical outcome trial in the Russian and Buryat regions of East Siberia. Methods: The study included 118 Russian (from Irkutsk) and 109 Buryat (from Ulan-Ude) patients with emergency admission for percutaneous coronary interventional treatment of acute coronary syndrome (ACS). The patients were stratified by the presence of the CYP2C19*2, CYP2C19*3, CYP2C19*17 alleles, and the VEGFR-2 rs2305948 allele. Safety and efficacy endpoints were analyzed 30 days following coronary stenting (CS). Results: There was no significant difference found in the Russian and Buryat patients in terms of the frequency of the CYP2C19*2 minor allele (10.2% in the Russian against 12.8% in the Buryat patients, odds ratio [OR] = 1.167, confidence interval [CI] 0.729-2.323). However, the frequency of the CYP2C19*3 allele was significantly higher in the Buryat patients than in the Russian patients (12.8% vs. 2.1%), OR = 5.600, CI 2.579-17.974; while in the Russian patients the frequency of the CYP2C19*17 allele was higher than the Buryat patients (23.3% in Russian patients vs. 10.1% in Buryat, OR = 2.500, CI 1.587-4.618). No significant differences were found in the prevalence of the VEGFR-2 rs2305948 alleles between the two groups of patient populations (12.5 in Buryat patients vs. 11.5% in Russian, OR = 1.040, CI 0.614-1.980). The Buryat patients were highly significantly more likely to experience adverse effects associated with the inefficacy of clopidogrel treatment, that is, early recurrent ischemic pains after CS, than the Russian patients (χ2 = 11.325, p < 0.001). Conclusion: The Buryat patients receiving clopidogrel treatment after CS have a reduced risk of small or large hemorrhages, and an increased risk of thrombotic complications compared with Caucasians. These results suggest that other antiplatelet drugs should be used for treating the Buryat patients with ACS.

Keywords: CYP2C19 gene variants; acute coronary syndrome; clopidogrel; coronary stenting; ethnic characteristics; the Buryats.

MeSH terms

  • Acute Coronary Syndrome / genetics*
  • Aged
  • Alleles
  • Asian People / genetics
  • Clopidogrel / adverse effects
  • Clopidogrel / therapeutic use
  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / metabolism
  • Ethnicity / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / therapeutic use
  • Polymorphism, Single Nucleotide / genetics
  • Russia / epidemiology
  • Siberia / epidemiology
  • Ticlopidine / therapeutic use
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-2
  • Ticlopidine