A common mutation in the gene for coagulation factor XIII-A (Val34Leu): A risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases

The role of a common polymorphism in the factor XIII A-subunit gene (FXIII Val34Leu) has been recently investigated as a protective genetic factor aga inst arterial and Venous thrombosis. In addition, the less frequent Leu34 a llele has been described as a risk factor for intracerebral hemorrhage. We evaluated the prevalence of this polymorphism by PCR in three case-control studies of patients diagnosed as having primary intracerebral hemorrhage (P CH, n =130), coronary heart diseases (CHD, n = 240; myocardial infarction/n o myocardial infarction, 120/120), and cerebrovascular diseases (CVD, n = 2 40; cerebral infarction/transient ischaemic attack, 120/120). The matched c ontrol groups consisted of patients admitted to the hospital without histor y of vascular disease. In addition, 200 healthy subjects were investigated. The frequency of the mutated allele (Leu34) was higher in patients with PC H than in controls (33.8% vs. 23.1%, P = 0.009) and lower in CHD and CVD pa tients compared to controls (18.1% vs. 25.2%, P = 0.010 and 17.3% vs. 24.2% , P = 0.011, respectively). Moreover, among the patients with CHD, the Leu3 4 allele was underrepresented in cases with myocardial infarction than with out (12.9% vs. 23.3%, P = 0.004) and than in controls (12.9% vs. 25.2%, P < 0.001). Similar findings were obtained in patients with CVD comparing the cases with cerebral infarction versus cases with transient ischaemic attack (12.5% vs. 22.1%, P = 0.008) and Versus controls (12.5% vs. 24.2%, P < 0.0 01), Finally, considering altogether the groups of ischaemic patients (CHD and CVD, n = 480), it was noted a trend towards a higher mean age of the cl inical onset in homozygotes for the Leu allele than in the wild types (P = 0.078). This study indicates that in our population possession of the FXIII Val34Leu mutation predisposes to the occurrence of primary intracerebral h emorrhage and protects against cerebral and myocardial infarction. A wider modulatory role in the progression and onset of atherothrombotic diseases c ould be ascribed to FXIII Val34Leu. (C) 2001 Wiley Liss, Inc.