title: A pharmacogenetic effect of factor XIII valine 34 leucine polymorphism on fibrinolytic therapy for acute myocardial infarction.
abstract: OBJECTIVE
  The aim of this study was to evaluate the pharmacogenetic role of the factor XIII (FXIII) valine 34 leucine (Val34Leu) polymorphism in the fibrinolytic therapy of acute myocardial infarction (MI).
  
  
  BACKGROUND
  Fibrinolytic therapy is an established treatment for acute MI, but up to 40% of treated patients do not achieve optimal tissue reperfusion. The FXIII Val34Leu polymorphism is one of the most relevant functional polymorphisms described in the haemostatic system. The common Leu34 allele associates with an increased FXIII-transglutaminase activity, which results in an increased and faster rate of fibrin stabilization.
  
  
  METHODS
  We genotyped this polymorphism in 293 consecutive MI patients (62 +/- 12 years; 231 males) from two different European populations. All patients were treated with standard doses of fibrinolytic drugs. Noninvasive assessment of the efficacy of coronary fibrinolysis was evaluated by serial electrocardiograms and creatine kinase time-activity curves. The clinical outcome was also re-evaluated at 24 h (death, reinfarction, or urgent revascularization).
  
  
  RESULTS
  Multivariate analysis showed that Leu34 carriers displayed a significantly less efficient fibrinolysis than carriers of Val/Val genotype (p = 0.021; odds ratio [OR] 1.90, 95% confidence interval [CI] 1.10 to 3.28). At 24 h, Leu34 allele carriers had the worst outcome (p = 0.006; OR 2.14, 95% CI 1.25 to 3.68). Interestingly, the combination of the Leu34 allele and nonsmoking status increased the risk of non-reperfusion criteria (p = 0.003, OR 3.77), and worse outcomes at 24 h (p = 0.001, OR 4.55).
  
  
  CONCLUSIONS
  In a large cohort of nonselected and consecutive acute MI patients from two different European populations, we show clinical evidence that the presence of the Leu34 allele reduces the efficacy of fibrinolytic therapy.
authors.affiliation: Cardiology Department, Hospital General Universitario, Alicante, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Marín
authors.forename: Rocío
authors.initials: R
authors.lastname: González-Conejero
authors.forename: Kaeng W
authors.initials: KW
authors.lastname: Lee
authors.forename: Javier
authors.initials: J
authors.lastname: Corral
authors.forename: Vanessa
authors.initials: V
authors.lastname: Roldán
authors.forename: Francisca
authors.initials: F
authors.lastname: López
authors.forename: Francisco
authors.initials: F
authors.lastname: Sogorb
authors.forename: Juan
authors.initials: J
authors.lastname: Caturla
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
mesh_terms: D000368:Aged; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D015912:Thrombolytic Therapy; D014633:Valine / Q000235:genetics*
chemical_list: D005176:Factor XIII; D007930:Leucine; D014633:Valine