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The association between abcb1 gene polymorphism and clopidogrel response variability in stroke ischemic: a cross
Rakhmad Hidayat1,2, Rizqi Amanda Nabilah3, Marc Fisher4
1Department of Neurology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. rhidayat.md@gmail.com.
Insights
The ABCB1 C1236T gene variant increases bleeding risk in ischemic stroke patients taking clopidogrel. Understanding these genetic variations can help personalize antiplatelet therapy.
Area of Science:
- Pharmacogenomics
- Cardiovascular Medicine
- Neurology
Background:
- Clopidogrel is a standard antiplatelet therapy for ischemic stroke, inhibiting adenosine diphosphate (ADP)-induced platelet aggregation.
- P-glycoprotein (P-gp), encoded by the ABCB1 gene, influences clopidogrel absorption and may affect treatment response.
- ABCB1 gene polymorphisms are implicated in inter-individual variability of drug response.
Purpose of the Study:
- To investigate the impact of ABCB1 gene polymorphisms (C3435T and C1236T) on clopidogrel response in ischemic stroke patients.
- To determine the genotype frequencies of ABCB1 polymorphisms within this patient cohort.
Main Methods:
- A cross-sectional study involving 124 ischemic stroke patients treated with clopidogrel.
- Assessment of ABCB1 C3435T and C1236T polymorphisms.
- Measurement of platelet aggregation using VerifyNow PRU to classify response (unresponsive, responsive, bleeding risk).
Main Results:
- 12.9% of patients were non-responsive, 49.5% responsive, and 41.9% at bleeding risk.
- The ABCB1 C1236T homozygote wildtype (CC) genotype showed a 3.76-fold increased risk of bleeding compared to other variants (p=0.008).
- Genotype frequencies for C3435T were 35.9% wildtype, 43.5% heterozygote, 16.9% variant; for C1236T: 17.8% wildtype, 39.5% heterozygote, 42.7% variant.
Conclusions:
- The ABCB1 C1236T homozygote wildtype genotype is significantly associated with an elevated bleeding risk in clopidogrel-treated ischemic stroke patients.
- The most prevalent genotype for ABCB1 C1236T was the homozygote variant, while for ABCB1 C3435T, it was the heterozygote.
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.
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