Correlation P2Y12 Genetic Polymorphism As Risk Factor of Clopidogrel Resistance in Indonesian Stroke Patients

Vasc Health Risk Manag. 2023 Jan 29:19:53-61. doi: 10.2147/VHRM.S386107. eCollection 2023.

Abstract

Background: Stroke is one of the highest causes of disability and mortality in several countries worldwide. Secondary prevention is important in the management of stroke. Clopidogrel is widely used in Asia as secondary prevention for ischemic stroke, even though several studies in Western show limited data related to clopidogrel resistance in Asia. This study aims to determine the correlation between P2Y12 genetic polymorphism and clopidogrel resistance in Indonesia.

Methods: This study was conducted on one-year duration, the subjects were chosen through the consecutive sampling method, all subjects were examined for genetics and resistance to clopidogrel. The data were analyzed through statistical analysis, a bivariate analysis was conducted to determine the correlation between several variables and the resistance variable. This study employed resistance diagnostic methods with VerifyNow. Polymorphism of receptor P2Y12 was tested with the Polymerase Chain Reaction method (PCR) and analysis of restriction fragment length polymorphism (RFLP). The genes tested in this study were G52T and C34T.

Results: The number of participants in this study was 112. Examination of gene P2Y12 showed that the majority was homozygote, wild-type C34T allele (67%), and G52T (66.1%). There was no significant correlation between clopidogrel resistance and gene G52T and C34T of P2Y12 (p > 0.05). Hb levels significantly correlated with P2Y12 G52T (p = 0.024). Meanwhile, Fatty Liver significantly correlated with P2Y12 C34T (p = 0.037).

Conclusion: Indonesia showed a low clopidogrel resistance rate and a very low C34T and G52T allele P2Y12 gene mutation, meaning that Indonesia had low mutations in the P2Y12. This is the cause of clopidogrel resistance in this study only 15%. Therefore, in a region with less clopidogrel resistance, examination of the P2Y12 gene would not give significant results.

Keywords: P2Y12; antiplatelet; clopidogrel resistance; stroke.

MeSH terms

  • Clopidogrel* / therapeutic use
  • Drug Resistance* / genetics
  • Humans
  • Indonesia
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Polymorphism, Genetic
  • Purinergic P2Y Receptor Antagonists / therapeutic use
  • Receptors, Purinergic P2Y12* / genetics
  • Risk Factors
  • Stroke* / diagnosis
  • Stroke* / drug therapy
  • Stroke* / genetics

Substances

  • Clopidogrel
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12

Grants and funding

The authors thank Universitas Indonesia for funding this research through the PUTI Grant. Contract number NKB-1566/UN2.RST/HKP.05.00/2020