Association of P2RY12 Gene Variants and Non-Genetic Factors With Clopidogrel Responsiveness in Vietnamese Patients After Percutaneous Coronary Intervention: A Cross-Sectional Study

Abstract

Background

Clopidogrel response varies significantly among individuals due to multiple influencing factors. This study aimed to investigate the associations between P2RY12 gene variants, non-genetic factors, and platelet aggregation in patients undergoing clopidogrel therapy and percutaneous coronary intervention.

Methods

We conducted a cross-sectional descriptive study involving 171 patients who successfully underwent coronary artery stenting and were treated with clopidogrel at two military hospitals in Vietnam. Platelet aggregation was assessed using the light transmission aggregometry (LTA) method, with clopidogrel resistance (CR) defined as maximal platelet aggregation > 50%. P2RY12 genetic polymorphisms (C34T-rs6785930 and G52T-rs6809699) were genotyped using Sanger sequencing.

Results

The allele frequencies were 74.56% (C) and 25.44% (T) for P2RY12 C34T, and 88.30% (G) and 11.70% (T) for P2RY12 G52T. Platelet aggregation progressively increased across the GG, GT, and TT genotypes of P2RY12 G52T (p = 0.03), with patients carrying the TT genotype exhibiting significantly higher platelet aggregation compared to other genotypes (p = 0.01). Among non-genetic factors, proton pump inhibitor (PPI) intake was associated with a significant increase in platelet aggregation (p = 0.03). The prevalence of clopidogrel resistance (CR) was 43.86%. Multivariate logistic regression analysis identified the T allele of P2RY12 C34T, reduced estimated glomerular filtration rate (eGFR), and PPI intake as significant risk factors for CR (OR = 2.24, 2.49, 4.01; p = 0.02, 0.049, 0.01, respectively).

Conclusions

The T allele of P2RY12 C34T was associated with an increased risk of CR. Among non-genetic factors, PPI intake significantly elevated platelet aggregation and, along with reduced eGFR, contributed to a higher risk of CR.