title: Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome.
abstract: OBJECTIVE
  Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations.
  
  
  METHODS
  Prospective study at Emergency Unit, Heart Institute (InCor), University of São Paulo.
  
  
  METHODS
  Intrahospital evolution and platelet aggregation in response to tirofiban were analyzed in relation to four glycoprotein mutations in 50 patients indicated for percutaneous coronary intervention: 17 (34%) with unstable angina and 33 (66%) with non-ST-segment elevation myocardial infarction. Platelet aggregation was analyzed using the Born method. Blood samples were obtained before and one hour after tirofiban infusion. Glycoproteins Ia (807C/T ), Ib (Thr/Met) , IIb (Ile/Ser ) and IIIa (PIA ) were the mutations selected.
  
  
  RESULTS
  Hypertension, dyslipidemia, diabetes, smoking, previous coronary artery disease and stroke were similar between the groups. Mutant glycoprotein IIIa genotypes had lower platelet aggregation before tirofiban administration than that of the wild genotype (41.0% ± 22.1% versus 55.9% ± 20.8%; P = 0.035). Mutant glycoprotein IIIa genotypes correlated moderately with lower platelet inhibition (r = -0.31; P = 0.030). After tirofiban administration, platelet glycoprotein Ia, Ib, IIb and IIIa mutations did not influence the degree of inhibition of platelet aggregation or intrahospital mortality.
  
  
  CONCLUSIONS
  Mutations of glycoproteins Ia, Ib, IIb and IIIa did not influence platelet aggregation in response to tirofiban in patients with unstable angina and non-ST-segment elevation myocardial infarction.
authors.affiliation: MD, PhD. Associate Professor, Department of Cardiopulmonology, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Antonio de Padua
authors.initials: Ade P
authors.lastname: Mansur
authors.affiliation: BSc, PhD. Biochemist, Department of Cardiopulmonology, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Roggerio
authors.affiliation: MD, PhD. Attending Physician, Department of Cardiopulmonology, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Júlio Yoshio
authors.initials: JY
authors.lastname: Takada
authors.affiliation: MD, MSc. Doctoral Student, Department of Cardiopulmonology, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Pérola Michelle Vasconcelos
authors.initials: PM
authors.lastname: Caribé
authors.affiliation: MD, PhD. Attending Physician, Department of Cardiopulmonology, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Solange Desirée
authors.initials: SD
authors.lastname: Avakian
authors.affiliation: BSc. Central Laboratory Director, Department of Cardiopulmonology, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Célia Maria Cassaro
authors.initials: CM
authors.lastname: Strunz
mesh_terms: D000077284:Abciximab; D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000235:genetics; D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000077542:Eptifibatide; D005260:Female; D005838:Genotype; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010455:Peptides / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000235:genetics; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D014443:Tyrosine; D000077466:Tirofiban; D000077542:Eptifibatide; D000077284:Abciximab