Does glycoprotein IIIa gene (Pl(A)) polymorphism influence clopidogrel resistance? : a study in older patients.
BACKGROUND
Clopidogrel is a potent antiplatelet drug used for secondary prevention after ischaemic cardiovascular or cerebrovascular events. In patients with aspirin (acetylsalicylic acid) intolerance or resistance, it is used as monotherapy. Recent data report that Pl(A) polymorphism of the glycoprotein IIIa gene may account for differences in aspirin-induced antiplatelet effects. An increased degree of platelet reactivity was also reported in Pl(A2) carriers compared with Pl(A1/A1) patients after administration of a clopidogrel 300mg loading dose.


OBJECTIVE
The aim of this study was to assess the modulatory effect of the Pl(A2) allele on platelet aggregation in patients taking long-term clopidogrel. M ETHODS: The prevalence of the Pl(A2) allele was assessed in 38 (21 males, 17 females; mean age 63 +/- 13 years) clopidogrel-resistant and 59 (26 males, 33 females; mean age 63 +/- 11 years) clopidogrel-responsive patients. The polymerase chain reaction-restriction fragment length polymorphism method was utilised to evaluate Pl(A) polymorphism. A Carat TX4 optical platelet aggregometer (Carat Diagnostics Ltd, Budapest, Hungary) was used to measure 5 and 10 micromol/L adenosine diphosphate-induced platelet aggregation.


RESULTS
Significantly more patients were taking combination antiplatelet therapy in the clopidogrel-resistant group than in the clopidogrel-responsive group (50% vs 30%, respectively). The prevalence of the Pl(A2) allele did not differ significantly between the two groups (0.09 vs 0.13), even after adjustment for combination therapy and various risk factors.


CONCLUSIONS
Our results show that carriers of the Pl(A2) allele do not have an increased risk of clopidogrel resistance. These findings and data from our previous studies suggest that patients with a Pl(A2) allele homozygosity may benefit from antiplatelet therapy based on clopidogrel rather than aspirin.
Papp
Elod
E
First Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary.
Havasi
Viktoria
V
Bene
Judit
J
Komlosi
Katalin
K
Talian
Gabor
G
Feher
Gergely
G
Horvath
Beata
B
Szapary
Laszlo
L
Toth
Kalman
K
Melegh
Bela
B
D000328:Adult; D000368:Aged; D000483:Alleles; D002545:Brain Ischemia / Q000517:prevention & control; D000077144:Clopidogrel; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000517:prevention & control; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077144:Clopidogrel; D013988:Ticlopidine