Relationship between clopidogrel-related polymorphisms and variable platelet reactivity at 1 year: A cohort study from Han Chinese

Abstract

Background: This study was designed to investigate the eff ect of clopidogrel-related gene polymorphisms on platelet reactivity
and clinical outcome in Chinese Han patients. Materials and Methods: Th ree hundred and thirty-six percutaneous coronary
intervention - treated patients were recruited and followed for 1 year. Blood samples were collected from all patients for DNA
genotyping. Th e platelet reactivity unit was measured by the VerifyNow technique. Th e CYP2C19*2, CYP2C19*3, CYP2C19*17,ATP-binding cassette subfamily B member 1, ITGB3, CYP2C9*3, CYP2B6*9, and P2Y12 alleles were assessed. Results: Th e clinical endpoints were related to previous heart disease history (11.90% vs. 28.57%, P = 0.017), stroke (12.24% vs. 16.67%, P = 0.039), and diabetes (27.55% vs. 52.38%, P = 0.047). High on-treatment platelet reactivity (HTPR) was frequent in advanced age (P = 0.019), male
gender (P = 0.016), hypertension (P = 0.033), and chronic renal failure (P = 0.040). Th ere were more endpoints in the CYP2C19*2 and P2Y12 mutant carriers (76.19% vs. 43.20%, P < 0.001; 50.00% vs. 35.71%, P = 0.001, respectively), whereas fewer in the CYP2C19*17 mutant carriers (11.90% vs. 56.46%, P = 0.001). CYP2C19*2 and P2Y12 polymorphism manifested HTPR (194.25 ± 45.91 vs.151.38 ± 58.14, P < 0.001; 180.33 ± 67.25 vs. 161.89 ± 56.49, P = 0.008, respectively), whereas CYP2C19*17 mutant improved platelet reactivity (97.17 ± 45.38 vs. 169.08 ± 57.15, P = 0.003). However, there were no further cardiovascular deaths in endpoint patients.Conclusion: In Han Chinese people of mainland China, clopidogrel-related gene polymorphisms are related to variable platelet reactivity after clopidogrel maintenance dosing, which infl uences major adverse cardiovascular events, without an eff ect on cardiac death.

Key words: Clopidogrel, polymorphism, VerifyNow