HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction

Factor XIII catalyzes the formation of covalent bounds between fibrin monomers, thus stabilizing the fibrin clot and increasing its resistance to fibrinolysis. The frequency of a frequent Val34Leu polymorphism in the FXIII A-subunit gene has been shown to be lower in patients with myocardial infarction or venous thrombosis than in controls, whereas it was higher in patients with hemorrhagic stroke than in controls. Our aim was to study the relation between brain infarction (BI) and the FXIII Val34Leu polymorphism in 456 patients consecutively recruited with a BI confirmed by MRI, and 456 matched controls. The distribution of genotypes was different in cases (63.2% Val/Val; 30.9% Val/Leu; 5.9% Leu/Leu) compared with controls (49.8% Val/Val; 42.8% Val/Leu; 7.4% Leu/Leu; P F .001). Carrying the Leu allele was associated with an OR of 0.58 (95% CI 5 0.44-0.75). A similar association was observed in cases and controls free of previous cardiovascular or cerebrovascular history (OR 5 0.51; 95% CI 5 0.36-0.73). No heterogeneity of this association was observed after stratification on the main BI subtypes. Adjustment for traditional vascular risk factors did not modify these findings. In addition, the effect of smoking was modified by the polymorphism (P 5 .05); the effect of smoking was weaker among Leu carriers than among noncarriers. In conclusion, there was a negative association of the FXIII Val34Leu polymorphism with BI, thus suggesting a protective effect of the Leu allele against thrombotic cerebral artery occlusion. In addition, our results suggest that among Leu carriers, the protective effect of the polymorphism outweighed the effect of smoking. (Blood. 2000;95:586-591)