Abstract
OBJECTIVES: The aim of this study was to evaluate the effect of polymorphisms affecting the clopidogrel metabolism (CYP3A4 IVS10+12G/A and CYP2C19*2) and the P2Y12 receptor (P2Y12 T744C) on modulating platelet function in acute coronary syndrome patients on dual antiplatelet treatment. BACKGROUND: Residual platelet reactivity (RPR) phenomenon on antiplatelet therapy requires clarification. P2Y12 T744C, CYP3A4 IVS10+12G/A and, in healthy individuals only, CYP2C19*2 polymorphisms have been investigated; however, the influence on platelet reactivity in a large population of high-risk vascular patients on dual antiplatelet treatment has not yet been elucidated. METHODS: A total of 1419 acute coronary syndrome patients on dual antiplatelet treatment were studied. Platelet function was evaluated by platelet-rich plasma aggregation. Electronic nanochips and restriction-fragment length polymorphism were used for analysis of polymorphisms. RESULTS: Only CYP2C19*2, out of the three investigated polymorphisms, is associated with higher platelet reactivity. Carriers of the *2 allele had significantly higher platelet aggregation values after arachidonic acid (AA; P=0.043), 2 μmol/l adenosine 5′ diphosphate (ADP; P
| Original language | English |
|---|---|
| Pages (from-to) | 1057-1064 |
| Number of pages | 8 |
| Journal | Pharmacogenetics and Genomics |
| Volume | 17 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2007 |
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Keywords
- Acute coronary syndrome
- ADP receptor P2Y
- Cytochrome P450
- Dual antiplatelet treatment
- Pharmacogenetics
- Polymorphism
- Residual platelet reactivity
ASJC Scopus subject areas
- Genetics
- Pharmacology
Cite this
Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10+12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual antiplatelet treatment in high-risk vascular patients. / Giusti, Betti; Gori, Anna Maria; Marcucci, Rossella; Saracini, Claudia; Sestini, Ilaria; Paniccia, Rita; Valente, Serafina; Antoniucci, Davide; Abbate, Rosanna; Gensini, Gian Franco.
In: Pharmacogenetics and Genomics, Vol. 17, No. 12, 12.2007, p. 1057-1064.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cytochrome P450 2C19 loss-of-function polymorphism, but not CYP3A4 IVS10+12G/A and P2Y12 T744C polymorphisms, is associated with response variability to dual antiplatelet treatment in high-risk vascular patients
AU - Giusti, Betti
AU - Gori, Anna Maria
AU - Marcucci, Rossella
AU - Saracini, Claudia
AU - Sestini, Ilaria
AU - Paniccia, Rita
AU - Valente, Serafina
AU - Antoniucci, Davide
AU - Abbate, Rosanna
AU - Gensini, Gian Franco
PY - 2007/12
Y1 - 2007/12
N2 - OBJECTIVES: The aim of this study was to evaluate the effect of polymorphisms affecting the clopidogrel metabolism (CYP3A4 IVS10+12G/A and CYP2C19*2) and the P2Y12 receptor (P2Y12 T744C) on modulating platelet function in acute coronary syndrome patients on dual antiplatelet treatment. BACKGROUND: Residual platelet reactivity (RPR) phenomenon on antiplatelet therapy requires clarification. P2Y12 T744C, CYP3A4 IVS10+12G/A and, in healthy individuals only, CYP2C19*2 polymorphisms have been investigated; however, the influence on platelet reactivity in a large population of high-risk vascular patients on dual antiplatelet treatment has not yet been elucidated. METHODS: A total of 1419 acute coronary syndrome patients on dual antiplatelet treatment were studied. Platelet function was evaluated by platelet-rich plasma aggregation. Electronic nanochips and restriction-fragment length polymorphism were used for analysis of polymorphisms. RESULTS: Only CYP2C19*2, out of the three investigated polymorphisms, is associated with higher platelet reactivity. Carriers of the *2 allele had significantly higher platelet aggregation values after arachidonic acid (AA; P=0.043), 2 μmol/l adenosine 5′ diphosphate (ADP; P
AB - OBJECTIVES: The aim of this study was to evaluate the effect of polymorphisms affecting the clopidogrel metabolism (CYP3A4 IVS10+12G/A and CYP2C19*2) and the P2Y12 receptor (P2Y12 T744C) on modulating platelet function in acute coronary syndrome patients on dual antiplatelet treatment. BACKGROUND: Residual platelet reactivity (RPR) phenomenon on antiplatelet therapy requires clarification. P2Y12 T744C, CYP3A4 IVS10+12G/A and, in healthy individuals only, CYP2C19*2 polymorphisms have been investigated; however, the influence on platelet reactivity in a large population of high-risk vascular patients on dual antiplatelet treatment has not yet been elucidated. METHODS: A total of 1419 acute coronary syndrome patients on dual antiplatelet treatment were studied. Platelet function was evaluated by platelet-rich plasma aggregation. Electronic nanochips and restriction-fragment length polymorphism were used for analysis of polymorphisms. RESULTS: Only CYP2C19*2, out of the three investigated polymorphisms, is associated with higher platelet reactivity. Carriers of the *2 allele had significantly higher platelet aggregation values after arachidonic acid (AA; P=0.043), 2 μmol/l adenosine 5′ diphosphate (ADP; P
KW - Acute coronary syndrome
KW - ADP receptor P2Y
KW - Cytochrome P450
KW - Dual antiplatelet treatment
KW - Pharmacogenetics
KW - Polymorphism
KW - Residual platelet reactivity
UR - http://www.scopus.com/inward/record.url?scp=38449103046&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38449103046&partnerID=8YFLogxK
U2 - 10.1097/FPC.0b013e3282f1b2be
DO - 10.1097/FPC.0b013e3282f1b2be
M3 - Article
C2 - 18004210
AN - SCOPUS:38449103046
VL - 17
SP - 1057
EP - 1064
JO - Pharmacogenetics and Genomics
JF - Pharmacogenetics and Genomics
SN - 1744-6872
IS - 12
ER -