Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome.
OBJECTIVE
To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel.


METHODS
Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan® and KASPar® assays. Platelet reactivity was measured with VerifyNow®.


RESULTS
Mean age of patients was 66±11 years and 182 (65.5%) patients presented ACS without ST-segment elevation. A total of 206 (74.1%) patients presented poor response to clopidogrel (PRC). CYP2C19*2 polymorphism (p=0.038) was associated with PRC in the univariate setting. In the multiple logistic regression analysis, the risk factors for PRC were the presence of CYP3A4*1B allele (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.01-16.34), age (OR 1.43; 95% CI 1.03-2.00), and body mass index (OR 4.05; 95% CI 1.21-13.43), whereas elevated hemoglobin was a protective factor. Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%).


CONCLUSIONS
CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables.
Department of Hospital Pharmacy Santa Lucía General University Hospital, Cartagena-Spain. henargl@gmail.com.
María Henar
MH
García-Lagunar
Luciano
L
Consuegra-Sánchez
Pablo
P
Conesa-Zamora
Javier
J
Ruiz-Cosano
Federico
F
Soria-Arcos
Luis
L
García de Guadiana
Pedro Cano
PC
Vivar
Juan Antonio
JA
Castillo-Moreno
Antonio
A
Melgarejo-Moreno
D054058:Acute Coronary Syndrome / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000368:Aged; D001792:Blood Platelets / Q000502:physiology*; D000077144:Clopidogrel / Q000627:therapeutic use*; D017023:Coronary Angiography; D003430:Cross-Sectional Studies; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors; D012372:ROC Curve; D012680:Sensitivity and Specificity
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19