Distribution of polymorphisms in the CYP2C19 and ABCB1 genes among patients with acute coronary syndrome in Lower Silesian population

Adv Clin Exp Med. 2019 Dec;28(12):1621-1626. doi: 10.17219/acem/110322.

Abstract

Background: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel administered to treat patients with acute coronary syndrome (ACS) is still being used. However, despite the proven efficacy of this treatment regimen, thromboembolic complications have been observed in some individuals. The reason for this phenomenon is linked to the so-called increased responsiveness of platelets despite high platelet resistance (HPR). A significant role in HPR is attributed to genetically determined differences in the absorption and activation of clopidogrel.

Objectives: The aim of the study was to assess the incidence of polymorphisms of the ABCB1 and CYPC19 genes that encode proteins involved in the absorption and metabolism of clopidogrel.

Material and methods: The analysis was performed in 199 consecutive patients from Lower Silesian voivodeship (Poland) who underwent coronary angioplasty with stenting for ACS. The single nucleotide polymorphism of the CYP2C19 and ABCB1 genes was performed using a mini sequencing or restriction fragment length polymorphism method.

Results: The results of this study revealed the high incidence of patients who may be unresponsive to antiplatelet treatment due to genetic causes. The CYPC19*2 allele in the form of homozygote or mutation heterozygote appeared in 26.1% of the study population. ABCB1 (C3435C> T) polymorphism was associated with 84% of patients. The total incidence of allelic disorders of low drug absorption and metabolism reached 14.6%.

Conclusions: The data obtained should prompt clinicians to use more recent antiplatelet agents (ticagrelor or prasugrel) first, instead of clopidogrel.

Keywords: ABCB1; CYP2C9; Lower Silesia; clopidogrel; polymorphism.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics*
  • Acute Coronary Syndrome* / drug therapy
  • Acute Coronary Syndrome* / genetics
  • Clopidogrel / therapeutic use*
  • Cytochrome P-450 CYP2C19 / genetics*
  • Genotype
  • Humans
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Poland
  • Polymorphism, Single Nucleotide*
  • Ticlopidine

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine