BACKGROUND: The CYP2C19 G681A single polymorphism has been proven to affect 
clopidogrel responsiveness. However, the effect of coexisting polymorphisms of 
other genes has not yet been reported in the Chinese population. This study 
investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on 
clopidogrel responsiveness and adverse clinical events in Chinese patients.
METHODS: In 577 Han Chinese patients undergoing stent placement because of acute 
coronary syndrome had platelet reactivity assessed by thromboelastography, and 
the CYP2C19 G681A and P2Y12 C34T polymorphisms were detected by the ligase 
detection reaction. Primary clinical endpoints included cardiovascular death, 
nonfatal myocardial infarction, target vessel revascularization, and stent 
thrombosis. The secondary clinical endpoints were thrombolysis in myocardial 
infarction bleeding. The follow-up period was 12 months.
RESULTS: Genotyping revealed 194 carriers of the wild type GG genotype of 
CYP2C19 and the wild type CC genotype of P2Y12 (group 1), 102 carriers of the 
wild type GG genotype of CYP2C19 and the mutational T allele of P2Y12 (group 2), 
163 carriers of the mutational A allele of CYP2C19 and the wild type CC genotype 
of P2Y12 (group 3), and 118 carriers of the mutational A allele of CYP2C19 and 
the mutational T allele of P2Y12 (group 4). Group 4 had the lowest 
ADP-inhibition (49.74 ± 32.61) and the highest prevalence of clopidogrel low 
response (29.7%) of the four groups. The rate of the composite of primary 
clinical endpoints increased more in group 4 (8.5%) than in the other three 
groups; the rate of composite primary endpoints in group 2 (2.9%) and group 3 
(3.7%) were not significantly different than that of group 1 (1.5%).
CONCLUSION: Coexisting polymorphisms of different genes affected clopidogrel 
responsiveness and clinical outcome more than single polymorphism in Chinese 
patients with acute coronary syndrome undergoing percutaneous coronary 
intervention.