title: A common mutation in the gene for coagulation factor XIII-A (VAL34Leu): a risk factor for primary intracerebral hemorrhage is protective against atherothrombotic diseases.
abstract: The role of a common polymorphism in the factor XIII A-subunit gene (FXIII Val34Leu) has been recently investigated as a protective genetic factor against arterial and venous thrombosis. In addition, the less frequent Leu34 allele 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 (PCH, n = 130), coronary heart diseases (CHD, n = 240; myocardial infarction/no myocardial infarction, 120/120), and cerebrovascular diseases (CVD, n = 240; cerebral infarction/transient ischaemic attack, 120/120). The matched control groups consisted of patients admitted to the hospital without history of vascular disease. In addition, 200 healthy subjects were investigated. The frequency of the mutated allele (Leu34) was higher in patients with PCH than in controls (33.8% vs. 23.1%, P = 0.009) and lower in CHD and CVD patients 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 Leu34 allele was underrepresented in cases with myocardial infarction than without (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 < 0.001). 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 clinical 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 hemorrhage and protects against cerebral and myocardial infarction. A wider modulatory role in the progression and onset of atherothrombotic diseases could be ascribed to FXIII Val34Leu.
authors.affiliation: Department of Biomedical Sciences and Advanced Therapies, Centre for the Study of Haemostasis and Thrombosis, University of Ferrara, Ferrara, Italy. cet@unife.it
authors.forename: D
authors.initials: D
authors.lastname: Gemmati
authors.forename: M L
authors.initials: ML
authors.lastname: Serino
authors.forename: A
authors.initials: A
authors.lastname: Ongaro
authors.forename: S
authors.initials: S
authors.lastname: Tognazzo
authors.forename: S
authors.initials: S
authors.lastname: Moratelli
authors.forename: R
authors.initials: R
authors.lastname: Resca
authors.forename: M
authors.initials: M
authors.lastname: Moretti
authors.forename: G L
authors.initials: GL
authors.lastname: Scapoli
mesh_terms: D017668:Age of Onset; D000483:Alleles; D019943:Amino Acid Substitution; D001161:Arteriosclerosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000235:genetics; D015897:Comorbidity; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics; D003920:Diabetes Mellitus / Q000453:epidemiology; D018450:Disease Progression; D005176:Factor XIII / Q000235:genetics*; D005787:Gene Frequency; D005796:Genes; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D002546:Ischemic Attack, Transient / Q000453:epidemiology / Q000235:genetics; D020125:Mutation, Missense; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D021122:Protein Subunits; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013927:Thrombosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D021122:Protein Subunits; D005176:Factor XIII