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Circ J. 2008 Jul;72(7):1165-9.

Coexisting polymorphisms of P2Y12 and CYP2C19 genes as a risk factor for persistent platelet activation with clopidogrel.

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1
Coronary Disease Department and II Catheterization Laboratory, Institute of Cardiology, Alpejska 42 str., 04-628 Warsaw, Poland. lmalek@ikard.pl

Abstract

BACKGROUND:

Coexisting polymorphisms of the genes affecting clopiogrel resistance may influence platelet activation.

METHODS AND 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.

PMID:
18577829
[Indexed for MEDLINE]
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