From theUnit of Molecular Vascular Medicine, Research School of Medicine,
University of Leeds, Leeds General Infirmary, Leeds, United Kingdom.
Correspondence to Professor Peter J Grant, Unit of Molecular Vascular Medicine, Leeds General Infirmary, Leeds LS1 3EX, UK. E-mail a.j.catto{at}leeds.ac.uk
Background and Purpose—A common
G-to-T point mutation (Val 34 Leu) in exon 2 of the
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.
© 1998 American Heart Association, Inc.
Original Contributions
Factor XIII Val 34 Leu
A Novel Association With Primary Intracerebral Hemorrhage
-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.
Key Words: factor XIII • fibrin • intracerebral hemorrhage • mutation • risk factors
This article has been cited by other articles:
 |
|
 |
|
  S. Debette and S. Seshadri Genetics of Atherothrombotic and Lacunar Stroke Circ Cardiovasc Genet, April 1, 2009; 2(2): 191 - 198. [Full Text] [PDF]
|
|
|
|
 |
|
 Wei Hsi Chen, Hung Sheng Lin, and Y.-F. Kao Type II Cryoglobulinemia and Brain Hemorrhage Clinical and Applied Thrombosis/Hemostasis, April 1, 2008; 14(2): 241 - 244. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Navarro-Nunez, M. L. Lozano, J. Rivera, J. Corral, V. Roldan, R. Gonzalez-Conejero, J. A. Iniesta, J. Montaner, V. Vicente, and C. Martinez The association of the {beta}1-tubulin Q43P polymorphism with intracerebral hemorrhage in men Haematologica, April 1, 2007; 92(4): 513 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gonzalez-Conejero, I. Fernandez-Cadenas, J. A. Iniesta, J. Marti-Fabregas, V. Obach, J. Alvarez-Sabin, V. Vicente, J. Corral, J. Montaner, and for the Proyecto Ictus Research Group Role of Fibrinogen Levels and Factor XIII V34L Polymorphism in Thrombolytic Therapy in Stroke Patients Stroke, September 1, 2006; 37(9): 2288 - 2293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Manno, J. L. D. Atkinson, J. R. Fulgham, and E. F. M. Wijdicks Emerging Medical and Surgical Management Strategies in the Evaluation and Treatment of Intracerebral Hemorrhage Mayo Clin. Proc., March 1, 2005; 80(3): 420 - 433. [Abstract] [PDF]
|
|
|
|
 |
|
 J. P. Casas, A. D. Hingorani, L. E. Bautista, and P. Sharma Meta-analysis of Genetic Studies in Ischemic Stroke: Thirty-two Genes Involving Approximately 18 000 Cases and 58 000 Controls Arch Neurol, November 1, 2004; 61(11): 1652 - 1661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. S. Ariens, T.-S. Lai, J. W. Weisel, C. S. Greenberg, and P. J. Grant Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms Blood, July 18, 2002; 100(3): 743 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gerlach, F. Tolle, A. Raabe, M. Zimmermann, A. Siegemund, and V. Seifert Increased Risk for Postoperative Hemorrhage After Intracranial Surgery in Patients With Decreased Factor XIII Activity: Implications of a Prospective Study Stroke, June 1, 2002; 33(6): 1618 - 1623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Weger, W. Renner, O. Stanger, O. Schmut, H. Deutschmann, T. C. Wascher, and A. Haas Role of Factor XIII Val34Leu Polymorphism in Retinal Artery Occlusion Stroke, December 1, 2001; 32(12): 2759 - 2761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Reiner, S. M. Schwartz, M. B. Frank, W.T. Longstreth Jr, L. A. Hindorff, G. Teramura, F. R. Rosendaal, L. K. Gaur, B. M. Psaty, D. S. Siscovick, et al. Polymorphisms of Coagulation Factor XIII Subunit A and Risk of Nonfatal Hemorrhagic Stroke in Young White Women Editorial Comment Stroke, November 1, 2001; 32(11): 2580 - 2587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Obach, M. Revilla, N. Vila, A. Cervera, and A. Chamorro {alpha}1-Antichymotrypsin Polymorphism: A Risk Factor for Hemorrhagic Stroke in Normotensive Subjects Stroke, November 1, 2001; 32(11): 2588 - 2591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Catto Genetic aspects of the hemostatic system in cerebrovascular disease Neurology, September 1, 2001; 57(90002): S24 - 30. [Abstract] [Full Text]
|
|
|
|
|
|
J. Corral, J. A. Iniesta, R. Gonzalez-Conejero, M. Villalon, and V. Vicente Polymorphisms of clotting factors modify the risk for primary intracranial hemorrhage Blood, May 15, 2001; 97(10): 2979 - 2982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Qureshi, S. Tuhrim, J. P. Broderick, H. H. Batjer, H. Hondo, and D. F. Hanley Spontaneous Intracerebral Hemorrhage N. Engl. J. Med., May 10, 2001; 344(19): 1450 - 1460. [Full Text] [PDF]
|
|
|
|
 |
|
 T C F Sykes, C Fegan, and D Mosquera Thrombophilia, polymorphisms, and vascular disease Mol. Pathol., December 1, 2000; 53(6): 300 - 306. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Hassan and H. S. Markus Genetics and ischaemic stroke Brain, September 1, 2000; 123(9): 1784 - 1812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Vila, V. Obach, M. Revilla, R. Oliva, and A. Chamorro {alpha}1-Antichymotrypsin Gene Polymorphism in Patients With Stroke Stroke, September 1, 2000; 31(9): 2103 - 2105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Lane and P. J. Grant Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease Blood, March 1, 2000; 95(5): 1517 - 1532. [Full Text] [PDF]
|
|
|
|
|
|
A. Elbaz, O. Poirier, S. Canaple, F. Chedru, F. Cambien, and P. Amarenco The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction Blood, January 15, 2000; 95(2): 586 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.P. Kohler and P.J. Grant The role of factor XIIIVal34Leu in cardiovascular disease QJM, February 1, 1999; 92(2): 67 - 72. [Full Text] [PDF]
|
|
|
|
|
|
A. J. Catto, H. P. Kohler, J. Coore, M. W. Mansfield, M. H. Stickland, and P. J. Grant Association of a Common Polymorphism in the Factor XIII Gene With Venous Thrombosis Blood, February 1, 1999; 93(3): 906 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Trumbo and M. C. Maurer Examining Thrombin Hydrolysis of the Factor XIII Activation Peptide Segment Leads to a Proposal for Explaining the Cardioprotective Effects Observed with the Factor XIII V34L Mutation J. Biol. Chem., June 30, 2000; 275(27): 20627 - 20631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sadasivan and V. C. Yee Interaction of the Factor XIII Activation Peptide with alpha -Thrombin. CRYSTAL STRUCTURE OF ITS ENZYME-SUBSTRATE ANALOG COMPLEX J. Biol. Chem., November 17, 2000; 275(47): 36942 - 36948. [Abstract] [Full Text] [PDF]
|
|