Abstract
Objective-Platelet α2A-adrenergic receptors (ARs) mediate platelet aggregation in response to sympathetic stimulation. The 6.3-kb variant of α2A-AR gene is associated with increased epinephrine-induced platelet aggregation in healthy volunteers. The cytochrome P450 2C19*2 (CYP2C19*2) loss-of-function allele influences P2Y12-mediated platelet inhibition and hence the rate of major adverse cardiovascular events. We assessed the influence of 6.3-kb α2A-AR gene variant on platelet aggregation and its interaction with CYP2C19*2 loss-of-function allele in patients with stable angina on aspirin and clopidogrel (dual antiplatelet therapy). Approach and Results-Aggregation to 5 increasing doses of epinephrine (from 0.156 to 10 μmol/L) was assessed in aggregation units by Multiplate Analyzer and platelet reactivity in P2Y12 reactivity units and % inhibition by VerifyNow P2Y12 assay before percutaneous revascularization. Gene polymorphisms were analyzed with TaqMan Drug Metabolism assay. Of 141 patients, aggregation was higher in 6.3-kb carriers (n=52) when compared with wild types (n=89) at all epinephrine doses (P2A-AR carriers. Percentage inhibition was lower (P=0.005) and P2Y12 reactivity units was higher (P=0.012) in CYP2C19*2 allele carriers. Higher P2Y12 reactivity units (P=0.037) and lower percentage inhibition (P=0.009) were observed in carriers of both 6.3-kb α2A-AR variant and CYP2C19*2 allele when compared with wild-type or with either mutation on its own. Conclusions-The 6.3-kb α2A-AR variant is associated with increased platelet reactivity to epinephrine and has an additive effect along with CYP2C19*2 loss-of-function allele on P2Y12-mediated platelet responses in patients with stable angina on dual antiplatelet therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 1314-1319 |
| Number of pages | 6 |
| Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Volume | 34 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- adrenergic alpha-2A receptors
- coronary artery disease
- CYP2C19, human
- genetic polymorphism
- platelet aggregation
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
α2A-adrenergic receptor polymorphism potentiates platelet reactivity in patients with stable coronary artery disease carrying the cytochrome P450 2C19*2 genetic variant. / Peace, Aaron J.; Mangiacapra, Fabio; Bailleul, Els; Delrue, Leen; Dierickx, Karen; Conte, Micaela; Puymirat, Etienne; Fraeymans, Anne Lies; Meeus, Pieter; Bartunek, Jozef; Volpe, Massimo; Barbato, Emanuele.
In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 34, No. 6, 2014, p. 1314-1319.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - α2A-adrenergic receptor polymorphism potentiates platelet reactivity in patients with stable coronary artery disease carrying the cytochrome P450 2C19*2 genetic variant
AU - Peace, Aaron J.
AU - Mangiacapra, Fabio
AU - Bailleul, Els
AU - Delrue, Leen
AU - Dierickx, Karen
AU - Conte, Micaela
AU - Puymirat, Etienne
AU - Fraeymans, Anne Lies
AU - Meeus, Pieter
AU - Bartunek, Jozef
AU - Volpe, Massimo
AU - Barbato, Emanuele
PY - 2014
Y1 - 2014
N2 - Objective-Platelet α2A-adrenergic receptors (ARs) mediate platelet aggregation in response to sympathetic stimulation. The 6.3-kb variant of α2A-AR gene is associated with increased epinephrine-induced platelet aggregation in healthy volunteers. The cytochrome P450 2C19*2 (CYP2C19*2) loss-of-function allele influences P2Y12-mediated platelet inhibition and hence the rate of major adverse cardiovascular events. We assessed the influence of 6.3-kb α2A-AR gene variant on platelet aggregation and its interaction with CYP2C19*2 loss-of-function allele in patients with stable angina on aspirin and clopidogrel (dual antiplatelet therapy). Approach and Results-Aggregation to 5 increasing doses of epinephrine (from 0.156 to 10 μmol/L) was assessed in aggregation units by Multiplate Analyzer and platelet reactivity in P2Y12 reactivity units and % inhibition by VerifyNow P2Y12 assay before percutaneous revascularization. Gene polymorphisms were analyzed with TaqMan Drug Metabolism assay. Of 141 patients, aggregation was higher in 6.3-kb carriers (n=52) when compared with wild types (n=89) at all epinephrine doses (P2A-AR carriers. Percentage inhibition was lower (P=0.005) and P2Y12 reactivity units was higher (P=0.012) in CYP2C19*2 allele carriers. Higher P2Y12 reactivity units (P=0.037) and lower percentage inhibition (P=0.009) were observed in carriers of both 6.3-kb α2A-AR variant and CYP2C19*2 allele when compared with wild-type or with either mutation on its own. Conclusions-The 6.3-kb α2A-AR variant is associated with increased platelet reactivity to epinephrine and has an additive effect along with CYP2C19*2 loss-of-function allele on P2Y12-mediated platelet responses in patients with stable angina on dual antiplatelet therapy.
AB - Objective-Platelet α2A-adrenergic receptors (ARs) mediate platelet aggregation in response to sympathetic stimulation. The 6.3-kb variant of α2A-AR gene is associated with increased epinephrine-induced platelet aggregation in healthy volunteers. The cytochrome P450 2C19*2 (CYP2C19*2) loss-of-function allele influences P2Y12-mediated platelet inhibition and hence the rate of major adverse cardiovascular events. We assessed the influence of 6.3-kb α2A-AR gene variant on platelet aggregation and its interaction with CYP2C19*2 loss-of-function allele in patients with stable angina on aspirin and clopidogrel (dual antiplatelet therapy). Approach and Results-Aggregation to 5 increasing doses of epinephrine (from 0.156 to 10 μmol/L) was assessed in aggregation units by Multiplate Analyzer and platelet reactivity in P2Y12 reactivity units and % inhibition by VerifyNow P2Y12 assay before percutaneous revascularization. Gene polymorphisms were analyzed with TaqMan Drug Metabolism assay. Of 141 patients, aggregation was higher in 6.3-kb carriers (n=52) when compared with wild types (n=89) at all epinephrine doses (P2A-AR carriers. Percentage inhibition was lower (P=0.005) and P2Y12 reactivity units was higher (P=0.012) in CYP2C19*2 allele carriers. Higher P2Y12 reactivity units (P=0.037) and lower percentage inhibition (P=0.009) were observed in carriers of both 6.3-kb α2A-AR variant and CYP2C19*2 allele when compared with wild-type or with either mutation on its own. Conclusions-The 6.3-kb α2A-AR variant is associated with increased platelet reactivity to epinephrine and has an additive effect along with CYP2C19*2 loss-of-function allele on P2Y12-mediated platelet responses in patients with stable angina on dual antiplatelet therapy.
KW - adrenergic alpha-2A receptors
KW - coronary artery disease
KW - CYP2C19, human
KW - genetic polymorphism
KW - platelet aggregation
UR - http://www.scopus.com/inward/record.url?scp=84901508632&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901508632&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.114.303275
DO - 10.1161/ATVBAHA.114.303275
M3 - Article
C2 - 24723553
AN - SCOPUS:84901508632
VL - 34
SP - 1314
EP - 1319
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 6
ER -