eNOS gene influences platelet phenotype in acute coronary syndrome patients on dual antiplatelet treatment.
Nitric Oxide (NO) plays a relevant role in regulating platelet recruitment and eNOS is the major isoform known to be expressed in platelets. Polymorphisms in the eNOS gene with a reduced NO availability might affect platelet phenotype. The aim of our study was to evaluate the role of eNOS-786T > C, 894G > T and 4a/4b polymorphisms in modulating platelet phenotype in 1442 acute coronary syndrome (ACS) patients on dual antiplatelet therapy, previously investigated in relation to platelet function. Platelet aggregation on platelet-rich plasma after collagen (2 microg/mL), ADP (10 microM) and arachidonic acid (AA) (1 mM) stimuli and the genetic analysis of eNOS polymorphisms were assessed. In subjects carrying the eNOS 4a and -786C alleles a significantly higher maximal platelet aggregation value after AA was found (p = 0.02 and p = 0.047, respectively). eNOS 4a but not -786C allele weakly influenced platelet aggregation after collagen stimulus (p = 0.05). eNOS 4a allele significantly and independently influenced AA-induced platelet aggregation (p = 0.01). A significantly higher percentage of patients with AA-induced high residual platelet reactivity (RPR) was found in subjects carrying both eNOS 4a and -786C allele (p = 0.03 and p = 0.04, respectively). At logistic multivariate analysis, the eNOS 4a allele significantly influenced the AA-induced high residual platelet reactivity (p = 0.02). This study evidences a role for eNOS gene in moderately, but significantly, modulating platelet phenotype in a high-risk population on dual antiplatelet treatment.
Fatini
Cinzia
C
Department of Medical and Surgical Critical Care, Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, University of Florence, 50134 Florence, Italy. cinziafatini@hotmail.com
Sticchi
Elena
E
Bolli
Paola
P
Marcucci
Rossella
R
Giusti
Betti
B
Paniccia
Rita
R
Gori
Anna Maria
AM
Gensini
Gian Franco
GF
Abbate
Rosanna
R
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D012044:Regression Analysis
D010975:Platelet Aggregation Inhibitors; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III