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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.
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.
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