Genetic polymorphisms of high platelet reactivity in Chinese patients with coronary heart disease under clopidogrel therapy

Abstract

Background: The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors, but the specific genes and other risk factors remain unclear. Objective: To investigate the incidence of high on-treatment platelet reactivity in coronary heart disease patients following clopidogrel therapy by analyzing the correlation between genetic polymorphisms and high on-treatment platelet reactivity. Setting: This study was conducted in the Chinese People’s Liberation Army (PLA) general hospital. Method: 578 patients with coronary heart disease undergoing percutaneous transluminal coronary intervention treatment were enrolled. They received dual antiplatelet therapy with aspirin (300 mg) plus clopidogrel (300 mg) over 24 h, or aspirin (100 mg/day) and clopidogrel (75 mg/day) over 3 days. Patients were divided into two groups according to the adenosine diphosphate inhibition rate. The follow-up lasted at least 12 months and adverse endpoint events were recorded. Main outcome measure: The single nucleotide polymorphisms were detected by MassArray genotyping system. Results: The incidence of HTPR was 15.74% in total, being higher in females than in males (24.29% vs. 13.01%, P < 0.01). Diabetes mellitus, homocysteine and high sensitivity C-reactive protein (hs-CRP) levels were significantly higher in the HTPR group than those in the non-HTPR group (P < 0.05). Polymorphisms of rs1057910 (OR 2.90, P = 0.003), rs2246709 (OR 0.69, P = 0.039), and rs776746 (OR 0.66, P = 0.034) were associated with the incidence of high on-treatment platelet reactivity. Female patients were prone to polymorphisms of rs1057910 (OR 3.24, P = 0.004) and rs776746 (OR 0.57, P = 0.025). Compared to non-high on-treatment platelet reactivity group, no differences in high reactivity group were observed with coexisting single nucleotide polymorphisms (14.6% vs. 14.8%, P > 0.05). The adverse endpoint events were significantly higher in the high on-treatment platelet reactivity group than in the non-treatment reactivity group. The survival analysis showed that high on-treatment platelet reactivity was significantly associated with the risk of the endpoint events (P = 0.0219). Conclusion: Gender (female), diabetes mellitus, high levels of homocysteine and hs-CRP were risk factors for high on-treatment platelet reactivity, and high reactivity was a strong predictor for adverse endpoint events in the coronary heart disease patients. The polymorphism of rs1057910 was a risk factor of high on-treatment platelet reactivity while rs2246709 and rs776746 polymorphisms were protective factors, and coexisting single nucleotide polymorphisms didn’t increase the incidence of high on-treatment platelet reactivity.