Factor XIII Val 34 Leu: a novel association with primary intracerebral hemorrhage.
OBJECTIVE
A common G-to-T point mutation (Val 34 Leu) in exon 2 of the alpha-subunit of the factor XIII is strongly negatively associated with the development of myocardial infarction. This result suggests that factor XIII Val 34 Leu is interfering with the formation of cross-linked fibrin. The role of factor XIII Val 34 Leu in the pathogenesis of cerebral infarction and primary intracerebral hemorrhage is unknown.


METHODS
Six hundred twelve patients with acute stroke, defined by World Health Organization criteria and cranial CT, and 436 age-matched control subjects free of cerebrovascular disease were genotyped for the factor XIII Val 34 Leu mutation. Venous blood was drawn for the determination of hemostatic variables and lipids. Factor XIII genotype was determined through a single-stranded conformational polymorphism technique and plasminogen activator inhibitor (PAI)-1 4G/5G promoter genotype by allele-specific polymerase chain reaction.


RESULTS
The mutation was more frequent in patients with primary intracerebral hemorrhage (n=62) (54.8%; P=.05) than in control subjects (41.7%) or in patients with cerebral infarction (n=529) (46.5%; P=.22). There was no relationship between PAI-1 levels and the PAI-1 4G/5G genotype.


CONCLUSIONS
There was a slightly higher incidence of factor XIII Val 34 Leu in patients with PICH. This may be related to impaired cross-linking of fibrin and/or coagulation proteins.
Catto
A J
AJ
Unit of Molecular Vascular Medicine, Research School of Medicine, University of Leeds, Leeds General Infirmary, United Kingdom. a.j.catto@leeds.ac.uk
Kohler
H P
HP
Bannan
S
S
Stickland
M
M
Carter
A
A
Grant
P J
PJ
D000368:Aged; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000235:genetics*; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007930:Leucine; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D014633:Valine
D005176:Factor XIII; D007930:Leucine; D014633:Valine