[The effects of cytochrome P450 2C19 genetic polymorphism on clopidogrel resistance and recent prognosis of patients with acute coronary syndrome].
OBJECTIVE
To investigate the relationship between cytochrome P450 (CYP) 2C19 genetic polymorphism and clopidogrel resistance(CR) in patients with acute coronary syndrome(ACS), and to assess the effects of genetic polymorphism at CYP2C19 (681G>A) on the prognosis of ACS patients.


METHODS
A total of 462 patients with ACS were enrolled and received loading dose clopidogrel(600 mg). The blood samples of patients were collected before and 24 hours after taking loading dose clopidogrel, then 5 µmol/L ADP-induced platelet aggregation ratio (PAR) was examined. Difference of two PAR ≤ 10% was defined as CR. Genomic DNA of patients were extracted from whole blood samples according to standard protocols and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to genotype the single nucleotide polymorphism of the CYP2C19 681G>A. According to whether the gene CYP2C19 681A was carried, patients were divided into two groups: wild type group and non-wild type group. After PCI treatment, patients were followed up for 6 months and major cardiac adverse events (MACE) happened during follow-up periods were recorded.


RESULTS
Totally 127 enrolled cases were finally defined as CR (27.5%) , the frequency of CYP2C19 681A in patients with CR was higher than that in patients without CR (46.9% vs 28.1%, P < 0.01) . The ratio of CR in wild type group were lower than non-wide type group (17.4% vs 36.1%, P < 0.01) . Binary logistic regression analysis indicated that gene CYP2C19 681A was a strong independent predictor for CR in patients with ACS (OR 3.642, P < 0.05). After 6 months of follow-up, Kaplan-Meier survival analysis showed patients of wild type group and non-wild type group had significantly different cumulative non-events survival rates (94.8% vs 89.6%, Log rank = 4.296, P = 0.038) .


CONCLUSIONS
The genetic polymorphism of CYP2C19 was associated with CR in patients with ACS. The mutation of CYP2C19 gene increased the risk of MACE in ACS patients undergoing PCI treatments and affected the patients' prognosis.
Medical College of Jinan University, Guangzhou 510632, China.
Shao-nan
SN
Li
Email: lz71826@163.com.
Zhen
Z
Liu
Yi
Y
Luo
Ping-an
PA
Chen
Xiao-ming
XM
Lei
Guang-lian
GL
Li
D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine