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Blood, Vol. 95 No. 2 (January 15), 2000:
pp. 586-591
The association between the Val34Leu polymorphism in the
factor XIII gene and brain infarction
Alexis Elbaz,
Odette Poirier,
Sandrine Canaple,
François Chédru,
François Cambien, and
Pierre Amarenco on behalf of the
GÉNIC investigators
INSERM Unité 360 (A.E.), INSERM U 525 (O.P., F.C.), Service de
Neurologie, Centre Hospitalier Universitaire d'Amiens (S.C.), Service
de Neurologie, Centre Hospitalier Général de Meaux (F.Ch.),
Service de Neurologie, Saint-Antoine Hospital and Lariboisiere
Hospital, Pierre and Marie Curie University (P.A.), and Formation de
Recherche en Neurologie Vasculaire (Association Claude Bernard) (P.A.),
Paris, France.
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 < .001). Carrying
the Leu allele was associated with an OR of 0.58 (95%
CI = 0.44-0.75). A similar association was observed in cases and
controls free of previous cardiovascular or cerebrovascular history
(OR = 0.51; 95% CI = 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 = .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.
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