The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction

Factor XIII catalyzes the formation of covalent bounds between fibrin monom ers, thus stabilizing the fibrin clot and increasing its resistance to fibr inolysis. The frequency of a frequent Val34Leu polymorphism in the FXIII A- subunit gene has been shown to be lower in patients with myocardial infarct ion or venous thrombosis than in controls, whereas it was higher in patient s with hemorrhagic stroke than in controls, Our aim was to study the relati on between brain infarction (BI) and the FXIII Val34Leu polymorphism in 456 patients consecutively recruited with a BI confirmed by MRI, and 456 match ed controls, The distribution of genotypes was different in cases (63.2% Va l/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<.001). Carrying the Leu allele was associate d with an OR of 0.58 (95% CI = 0.44-0.75). A similar association was observ ed in cases and controls free of previous cardiovascular or cerebrovascular history (OR = 0.51; 95% CI = 0.36-0.73). No heterogeneity of this associat ion was observed after stratification on the main BI subtypes. Adjustment f or traditional vascular risk factors did not modify these findings. In addi tion, the effect of smoking was modified by the polymorphism (P=.05); the e ffect of smoking was weaker among Leu carriers than among noncarriers. In c onclusion, there was a negative association of the FXIII Val34Leu polymorph ism with Ri, 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 t he effect of smoking.