OBJECTIVES: This study assessed the effect of pharmacogenetics on the 
antiplatelet effect of clopidogrel.
BACKGROUND: Variability in clopidogrel response might be influenced by 
polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] 
family), transport proteins (P-glycoprotein) and/or target proteins for the drug 
(adenosine diphosphate-receptor P2Y12).
METHODS: Sixty patients undergoing elective percutaneous coronary intervention 
in the randomized PRINC (Plavix Response in Coronary Intervention) trial had 
platelet function measured using the VerifyNow P2Y12 analyzer after a 600-mg or 
split 1,200-mg loading dose and after a 75- or 150-mg daily maintenance dosage. 
Polymerase chain reaction-based genotyping evaluated polymorphisms in the 
CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes.
RESULTS: CYP2C19*1*1 carriers had greater platelet inhibition 2 h after a 600-mg 
dose (median: 23%, range: 0% to 66%), compared with platelet inhibition in 
CYP2C19*2 or *4 carriers (10%, 0% to 56%, p = 0.029) and CYP2C19*17 carriers 
(9%, 0% to 98%, p = 0.026). CYP2C19*2 or *4 carriers had greater platelet 
inhibition with the higher loading dose than with the lower dose at 4 h (37%, 8% 
to 87% vs. 14%, 0% to 22%, p = 0.002) and responded better with the higher 
maintenance dose regimen (51%, 15% to 86% vs. 14%, 0% to 67%, p = 0.042).
CONCLUSIONS: Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet 
inhibition after a clopidogrel 600-mg loading dose but responded to higher 
loading and maintenance dose regimens. Genotyping for the relevant gene 
polymorphisms may help to individualize and optimize clopidogrel treatment. 
(Australia New Zealand Clinical Trials Registry; ACTRN12606000129583).