PIK3CG single nucleotide polymorphisms are associated with poor responsiveness to clopidogrel and increased risk of ischemia in patients with coronary heart disease

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Abstract

Background:

This study explores the associations between PIK3CG single nucleotide polymorphisms (SNPs, rs1129293 and rs17398575) and patient responsiveness to clopidogrel to evaluate the risks of ischemia in patients with coronary heart disease (CHD).

Methods:

The study consisted of 513 CHD patients who received clopidogrel as part of antiplatelet therapy, after percutaneous coronary intervention. According to the patient responsiveness to clopidogrel, the subjects were assigned to either clopidogrel-resistant (CR) or clopidogrel-sensitive (CS) groups. CR group was determined by patients’ platelet aggregation rate of ≥70% and poor responsiveness to clopidogrel, and CS group by patients’ platelet aggregation rates of <70% and good responsiveness to clopidogrel. Polymerase chain reaction using TaqMan probe was employed to detect PIK3CG polymorphism. Haplotype and linkage disequilibrium analyses were performed. Prognosis analysis was performed using the Kaplan-Meier curve.

Results:

Significant difference was found in genotype and rs1129293 and rs17398575 allele frequency between the CR and CS groups. Haplotype analysis indicated that the frequency of TG allele was higher in the CR group compared with the CS group, and the frequency of CA allele was lower in the CR group compared with the CS group. Patients with rs1129293 CT + TT genotype and T allele, rs1129293 AG + GG genotype and G allele exhibited an increased CR risk. Logistic regression analysis determined hypertension history as an independent risk factor for CR. The Kaplan-Meier curve suggests that distribution curve of cumulative probability nonischemic events was different between patients with rs1129293 and rs17398575 alleles. Stable CHD patients with TT genotype of rs1129293 allele and GG genotype of rs17398575 allele showed poorer prognosis compared to those with other genotypes and patients with acute coronary syndromes.

Conclusion:

A positive correlation may exist between PIK3CG SNPs (rs1129293 and rs17398575) and patients with poor responsiveness to clopidogrel. These findings show that this factor may contribute to an increased risk of ischemia in patients suffering from CHD.

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