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

Rakhmad Hidayat1,2,3, Al Rasyid2,3, Salim Harris2,3

  • 1Doctoral Program in Medical Sciences Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

Insights

In Indonesia, P2Y12 gene mutations are rare, leading to low clopidogrel resistance. Genetic testing for P2Y12 is unlikely to predict resistance in this population.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Clinical Pharmacy

Background:

  • Stroke is a leading cause of disability and mortality globally.
  • Secondary prevention of ischemic stroke is crucial.
  • Clopidogrel is a common secondary prevention drug in Asia, but resistance data is limited.

Purpose of the Study:

  • To investigate the correlation between P2Y12 genetic polymorphism and clopidogrel resistance in Indonesian patients.
  • To assess the prevalence of specific P2Y12 gene variants (G52T and C34T) in the Indonesian population.
  • To understand the implications of genetic variations on clopidogrel efficacy for stroke prevention.

Main Methods:

  • A one-year prospective study involving 112 participants.
  • Consecutive sampling method for subject selection.
  • Genetic analysis using Polymerase Chain Reaction (PCR) and restriction fragment length polymorphism (RFLP) for P2Y12 G52T and C34T variants.
  • Clopidogrel resistance assessed using the VerifyNow assay.
  • Bivariate statistical analysis to determine correlations.

Main Results:

  • The majority of participants were homozygote wild-type for C34T (67%) and G52T (66.1%) P2Y12 alleles.
  • No significant correlation was found between clopidogrel resistance and P2Y12 G52T or C34T gene variants (p > 0.05).
  • Hemoglobin levels correlated significantly with P2Y12 G52T (p = 0.024), and Fatty Liver correlated significantly with P2Y12 C34T (p = 0.037).

Conclusions:

  • Indonesia exhibits a low rate of clopidogrel resistance (15%) and minimal P2Y12 gene mutations (C34T and G52T).
  • The low prevalence of these specific P2Y12 polymorphisms explains the limited clopidogrel resistance observed.
  • Genetic testing for P2Y12 G52T and C34T may not be clinically significant for predicting clopidogrel resistance in Indonesian populations.
Abstract

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