Coexisting polymorphisms of P2Y12 and CYP2C19 genes as a risk factor for persistent platelet activation with clopidogrel.
BACKGROUND
Coexisting polymorphisms of the genes affecting clopiogrel resistance may influence platelet activation.


RESULTS
In 105 patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention, platelet function was measured and registered as closure time in the test with collagen and adenosine diphosphate (CADP-CT). Patients were followed for 12 months for death or recurrent myocardial infarction (MI). Genotyping revealed 7 carriers of both the C allele of P2Y12 and A allele of CYP2C19 (group 1), 14 carriers of the T allele of P2Y12 and A allele of CYP2C19 (group 2), 17 carriers of the C allele of P2Y12 and G allele of CYP2C19 (group 3) and 67 carriers of the T allele of P2Y12 and G allele of CYP2C19 (controls). The median CADP-CT value was significantly lower in group 1 than in group 2 or 3 (p<0.01) or controls (p<0.002), but did not differ between group 2 or 3 and controls. There were 2 cardiovascular deaths and 4 MI during follow-up, and the median CADP-CT value was lower in these patients (p=0.09).


CONCLUSIONS
Coexisting, rather then single, polymorphisms of different genes may be related to persistent platelet activation while on clopidogrel, which raises concern about harm in patients with ACS.
Malek
Lukasz A
LA
Coronary Disease Department and II Catheterization Laboratory, Institute of Cardiology, Alpejska 42 str., 04-628 Warsaw, Poland. lmalek@ikard.pl
Kisiel
Bartlomiej
B
Spiewak
Mateusz
M
Grabowski
Marcin
M
Filipiak
Krzysztof J
KJ
Kostrzewa
Grazyna
G
Huczek
Zenon
Z
Ploski
Rafal
R
Opolski
Grzegorz
G
D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058925:Receptors, Purinergic P2Y12; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine