A pharmacogenetic effect of factor XIII valine 34 leucine polymorphism on fibrinolytic therapy for acute myocardial infarction.
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.
Marín
Francisco
F
Cardiology Department, Hospital General Universitario, Alicante, Spain.
González-Conejero
Rocío
R
Lee
Kaeng W
KW
Corral
Javier
J
Roldán
Vanessa
V
López
Francisca
F
Sogorb
Francisco
F
Caturla
Juan
J
Lip
Gregory Y H
GY
Vicente
Vicente
V
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*
D005176:Factor XIII; D007930:Leucine; D014633:Valine