Glycoprotein IIIA gene (PlA) polymorphism and aspirin resistance: is there any correlation?
BACKGROUND
Platelet glycoprotein (GP) IIb/IIIa receptors play an inevitable role in platelet aggregation. The GP IIIa gene is polymorphic (PlA1/PlA2) and the presence of a PlA2 allele might be associated with an increased risk for acute coronary syndrome (ACS).


OBJECTIVE
To examine the prevalence of the PlA2 allele in patients with ACS and in subjects with or without aspirin resistance.


METHODS
The prevalence of the PlA2 allele was assessed in 158 patients with ACS and PlA2 compared with its prevalence in 199 healthy volunteers. The antiplatelet efficacy of aspirin was examined in all patients with ACS, as well as in 69 individuals who had suffered ischemic stroke and in 58 high-risk subjects without any known ischemic vascular events.


RESULTS
PlA2 prevalence was significantly higher in patients with ACS (59/158) than in the control group (51/199; p < 0.05). Carriers of the PlA2 allele had a significantly higher risk of developing ACS, even after an adjustment to the risk factors (OR 5.74; 95% CI 1.75 to 18.8; p = 0.004). The occurrence of the PlA2 allele was significantly higher among patients with aspirin resistance than in subjects who demonstrated an appropriate response to the drug (allele frequencies, 0.21 vs 0.14; p < 0.05). All patients homozygous for the PlA2 allele had an inadequate platelet response to aspirin.


CONCLUSIONS
Our results support the hypothesis that carriers of the PlA2 allele might have an increased risk for ACS. PlA2 homozygosity was associated with an inadequate response to aspirin therapy. Our data further suggest that patients with PlA2 allele homozygosity might benefit from antiplatelet therapy based on adenosine diphosphate antagonists throughout secondary treatment for prevention of ACS.
Papp
Elod
E
First Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary. elod.papp@aok.pte.hu
Havasi
Viktoria
V
Bene
Judit
J
Komlosi
Katalin
K
Czopf
Laszlo
L
Magyar
Eva
E
Feher
Csaba
C
Feher
Gergely
G
Horvath
Beata
B
Marton
Zsolt
Z
Alexy
Tamas
T
Habon
Tamas
T
Szabo
Levente
L
Toth
Kalman
K
Melegh
Bela
B
D000328:Adult; D000368:Aged; D000483:Alleles; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D050171:Dyslipidemias / Q000150:complications; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006814:Hungary; D006973:Hypertension / Q000150:complications; D039661:Integrin beta3 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D009765:Obesity / Q000150:complications; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking; D013577:Syndrome
D039661:Integrin beta3; D001241:Aspirin