The association between abcb1 gene polymorphism and clopidogrel response variability in stroke ischemic: a cross sectional study

BMC Neurol. 2024 Jun 24;24(1):216. doi: 10.1186/s12883-024-03723-y.

Abstract

Background: Clopidogrel has been the primary choice of antiplatelet in ischemic stroke that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. P-glycoprotein (P-gp) multidrug resistance-1 (MDR1) is a transmembrane efflux transporter in intestinal cells that plays a significant role in clopidogrel absorption, therefore may affect platelet aggregation. P-gp is encoded by the ABCB1 gene. This study aims to evaluate the effect of ABCB1 polymorphism on clopidogrel response variability in ischemic stroke patients and its genotype frequency.

Methods: A cross-sectional study was conducted in ischemic stroke patients who received clopidogrel between 2020 and 2023 in RSUI/RSCM. All subjects were assessed for ABCB1 polymorphisms C3435T and C1236T. Platelet aggregation were measured using VerifyNow PRU. Clopidogrel response variability was classified into unresponsive (> 208 PRU), responsive (95-208 PRU), and bleeding risk (< 95 PRU).

Results: 124 subjects enrolled in this study, with 12,9% of subjects classified as non-responsive/resistant, 49,5% as responsive, and 41,9% as bleeding risk. ABCB1 C1236T homozygote wildtype (CC) was associated with 3,76 times higher bleeding risk than other variants (p = 0,008; 95%CI 1,41 - 10,07). Genotype frequency of ABCB1 C3435T homozygote wildtype, heterozygote, and homozygote variants were 35,9%, 43,5% and 16,9%, respectively; while the genotype frequency of ABCB1 C1236T were 17,8%, 39,5%, and 42,7%, respectively.

Conclusion: ABCB1 C1236T homozygote wildtype was associated with 3,76 times higher bleeding risk than other variants. The most common genotype frequency of ABCB1 C1236T was homozygote variant; while for ABCB1 C3435T was heterozygote.

Keywords: ABCB1; Clopidogrel; Response variability.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B* / genetics
  • Aged
  • Clopidogrel* / administration & dosage
  • Clopidogrel* / therapeutic use
  • Cross-Sectional Studies
  • Female
  • Genotype
  • Humans
  • Ischemic Stroke* / drug therapy
  • Ischemic Stroke* / genetics
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / genetics
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Polymorphism, Single Nucleotide / genetics

Substances

  • Clopidogrel
  • ATP Binding Cassette Transporter, Subfamily B
  • ABCB1 protein, human
  • Platelet Aggregation Inhibitors