title: Platelet aggregability is modulated by eNOS locus in non-type 2 diabetic patients with acute coronary syndrome.
abstract: OBJECTIVE
  Platelet nitric oxide (NO) synthesis is compromised in patients with acute coronary syndrome (ACS), and platelet NO availability may be critically relevant in determining the extent of thrombosis in ACS patients. It has been demonstrated that an impaired responsiveness to the antiaggregatory effects of NO may affect platelet dysfunction in diabetic patients with ACS. Since NO availability may be genetically determined, we have investigated the role of endothelial nitric oxide synthase (eNOS) gene in influencing platelet aggregability in relation to the presence (n=247) or absence (n=883) of type 2 diabetes in ACS patients.
  
  
  RESULTS
  We have genotyped 1130 consecutive high risk ACS patients on dual antiplatelet therapy, previously investigated in relation to platelet function. eNOS 4a allele frequency was significantly higher in diabetic vs. non-diabetic patients (p=0.02). In non-diabetic patients the eNOS 4a allele significantly modulated platelet aggregability in response to arachidonic acid (AA), but not to collagen and adenosine diphosphate (ADP) stimulus, after Bonferroni correction for multiple testing. After adjustment for age, gender, smoking habit, hypertension and ejection fraction ≤40%, the eNOS 4a allele remained significantly and independently associated with platelet aggregability in response to AA stimulus [β (SE)=0.17 (0.07), p=0.01]. When platelet aggregation values were considered according to the presence or absence of high residual platelet reactivity (RPR) eNOS 4a, but not -786C and 894T, allele was significantly associated with RPR by AA stimulus. The haplotype reconstruction analysis for eNOS gene showed that the -786C/894G/4a and -786C/894G/4b haplotypes significantly influenced platelet aggregation after AA stimulus.
  
  
  CONCLUSIONS
  Our study indicates that eNOS 4a allele, may be a determinant of higher platelet aggregability and residual platelet reactivity in non-diabetic ACS patients.
authors.affiliation: Department of Medical and Surgical Critical Care, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy. cinziafatini@hotmail.com
authors.forename: C
authors.initials: C
authors.lastname: Fatini
authors.forename: E
authors.initials: E
authors.lastname: Sticchi
authors.forename: P
authors.initials: P
authors.lastname: Bolli
authors.forename: R
authors.initials: R
authors.lastname: Marcucci
authors.forename: B
authors.initials: B
authors.lastname: Giusti
authors.forename: R
authors.initials: R
authors.lastname: Paniccia
authors.forename: A M
authors.initials: AM
authors.lastname: Gori
authors.forename: G F
authors.initials: GF
authors.lastname: Gensini
authors.forename: R
authors.initials: R
authors.lastname: Abbate
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000150:complications / Q000235:genetics*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016718:Arachidonic Acid / Q000494:pharmacology; D015331:Cohort Studies; D003094:Collagen / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000235:genetics*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D010974:Platelet Aggregation / Q000235:genetics* / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D052250:Nitric Oxide Synthase Type III