title: Smoking and the platelet fibrinogen receptor glycoprotein IIb/IIIA PlA1/A2 polymorphism interact in the risk of lacunar stroke and midterm survival.
abstract: OBJECTIVE
  Smoking, increased fibrinogen levels, and platelet activation are related to the risk of ischemic stroke. The platelet fibrinogen receptor glycoprotein (Gp) IIb/IIIa Pl(A1/A2) polymorphism affects the binding of platelets to fibrinogen and is suggested to interact with smoking.
  
  
  METHODS
  We explored the association of smoking and the Pl(A1/A2) polymorphism with ischemic stroke and survival in the Stroke Aging Memory cohort, comprising 486 consecutive patients (55 to 85 years old) who were analyzed 3 months after an ischemic stroke and followed up for 15 months. Stroke subtype determined by magnetic resonance imaging and GpIIb/IIIa Pl(A1/A2) genotype data were available for 272 patients.
  
  
  RESULTS
  In multivariate analysis, smoking was the only factor related to the risk of lacunar infarcts (odds ratio [OR]=1.87, 95% CI=1.05 to 3.31; P=0.033), and it was also a predictor of death (n=24, 8.8%) at 15 months (OR=5.13, 95% CI=1.61 to 16.36; P=0.006), along with age (OR=1.10, 95% CI=1.01 to 1.19; P=0.008). The GpIIb/IIIa Pl(A1/A2) polymorphism alone showed no association with stroke subtype or survival. However, there was a smoking-by-genotype association with the risk of lacunar infarcts (OR=2.10, 95% CI=0.90 to 4.89; P=0.087) and with survival (OR=2.78, 95% CI=0.89 to 8.61; P=0.077). Among younger (55 to 69 years) stroke patients, smokers carrying the Pl(A2) allele were at a higher (OR=5.81, 95% CI=1.26 to 26.80; P=0.024) risk of lacunar infarcts than noncarrier smokers (OR=3.12, 95% CI=1.06 to 9.24; P=0.039). The effect of Pl(A2) and smoking combined on survival was also stronger (OR=8.86, 95% CI=1.68 to 46.55; P=0.010) than the effect of smoking alone (OR=5.06, 95% CI=1.20 to 21.35; P=0.027).
  
  
  CONCLUSIONS
  Our results indicate that prothrombotic genetic factors may interact with smoking by modifying the stroke phenotype and affecting midterm survival.
authors.affiliation: Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland.
authors.forename: Niku K J
authors.initials: NK
authors.lastname: Oksala
authors.forename: Maarit
authors.initials: M
authors.lastname: Heikkinen
authors.forename: Jussi
authors.initials: J
authors.lastname: Mikkelsson
authors.forename: Tarja
authors.initials: T
authors.lastname: Pohjasvaara
authors.forename: Markku
authors.initials: M
authors.lastname: Kaste
authors.forename: Timo
authors.initials: T
authors.lastname: Erkinjuntti
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001777:Blood Coagulation / Q000235:genetics; D020520:Brain Infarction / Q000235:genetics* / Q000401:mortality*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology*; D015996:Survival Rate
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex