From the Cardiovascular Health Research Unit (W.T.L., D.S.S., S.M.S.,
B.M.P., T.E.R., T.D.K.) and the Departments of Neurology (W.T.L.),
Epidemiology (W.T.L., D.S.S., S.M.S., B.M.P., T.D.K.), Medicine (D.S.S.,
B.M.P., T.D.K.), Health Services (B.M.P., T.D.K.), and Biostatistics (T.E.R.),
University of Washington, Seattle, Wash; the Hemostasis and Thrombosis
Research Centre (F.R.R., H.L.V., P.H.R.) and Department of Clinical
Epidemiology (F.R.R.), University Hospital Leiden, Leiden, the Netherlands;
and the Laboratory for Experimental Internal Medicine, Academic Medical
Center, University of Amsterdam (The Netherlands) (P.H.R.).
Correspondence to W.T. Longstreth, Jr, MD, Department of Neurology, Box 359775, Harborview Medical Center, 325 Ninth Ave, Seattle, WA 98104-2499. E-mail wl{at}u.washington.edu
Background and Purpose—Factor V
Leiden and a prothrombin gene variant, G20210A, are mutations
associated with a thrombotic risk. The aim of our study was to assess
whether these mutations increase the risk of stroke in women under 45
years of age.
Methods—We conducted a case-control study in western Washington
state. Case patients were women aged 18 to 44 years with a first stroke
(n=106). Control subjects were women without stroke recruited from the
same region by use of random-digit telephone dialing (n=391). All were
interviewed and provided blood specimens, which were genotyped
for these mutations.
Results—Factor V Leiden was found in 0.9% of case patients, a
single patient with a subarachnoid hemorrhage, and in
4.1% of control subjects. The odds ratio (OR) for any stroke was 0.2
(95% confidence interval [CI], 0.03 to 1.7). The prothrombin variant
was found in 1.9% of case patients, 1 with a venous stroke and 1 with
an ischemic stroke, and in 1.6% of control subjects. The OR
for any stroke was 1.48 (95% CI, 0.14 to 9.17). ORs for stroke types
were also not statistically significant.
Conclusions—In this study, neither factor V Leiden nor the
prothrombin variant (G20210A) was an important risk factor for stroke
in young women. In this setting, screening for these mutations cannot
be recommended. Unanswered by this study is whether screening would be
useful in select patients, such as those with a strong family history
of thrombophilia or those with venous strokes.
© 1998 American Heart Association, Inc.
Original Contributions
Risk of Stroke in Young Women and Two Prothrombotic Mutations: Factor V Leiden and Prothrombin Gene Variant (G20210A)
Key Words: cerebrovascular disorders • mutation • factor V • prothrombin
This article has been cited by other articles:
 |
|
 |
|
  G. Celiker, U. Can, H. Verdi, A. C. Yazici, N. Ozbek, and F. B. Atac Prevalence of Thrombophilic Mutations and ACE I/D Polymorphism in Turkish Ischemic Stroke Patients Clinical and Applied Thrombosis/Hemostasis, August 1, 2009; 15(4): 415 - 420. [Abstract] [PDF]
|
|
|
|
 |
|
 G. W. Albers, P. Amarenco, J. D. Easton, R. L. Sacco, and P. Teal Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 630S - 669S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gokben, A. Tosun, N. Bayram, G. Serdaroglu, M. Polat, K. Kavakli, and H. Tekgul Arterial Ischemic Stroke in Childhood: Risk Factors and Outcome in Old Versus New Era J Child Neurol, October 1, 2007; 22(10): 1204 - 1208. [Abstract] [PDF]
|
|
|
|
 |
|
 R. L. Sacco, R. Adams, G. Albers, M. J. Alberts, O. Benavente, K. Furie, L. B. Goldstein, P. Gorelick, J. Halperin, R. Harbaugh, et al. Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline. Circulation, March 14, 2006; 113(10): e409 - e449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Sacco, R. Adams, G. Albers, M. J. Alberts, O. Benavente, K. Furie, L. B. Goldstein, P. Gorelick, J. Halperin, R. Harbaugh, et al. Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association Council on Stroke: Co-Sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline. Stroke, February 1, 2006; 37(2): 577 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Lalouschek, M. Schillinger, K. Hsieh, G. Endler, S. Tentschert, W. Lang, S. Cheng, and C. Mannhalter Matched Case-Control Study on Factor V Leiden and the Prothrombin G20210A Mutation in Patients With Ischemic Stroke/Transient Ischemic Attack Up to the Age of 60 Years Stroke, July 1, 2005; 36(7): 1405 - 1409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Altarescu, D. F. Moore, and R. Schiffmann Effect of genetic modifiers on cerebral lesions in Fabry disease Neurology, June 28, 2005; 64(12): 2148 - 2150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Gwinn-Hardy and V. Dawson Genomics-Proteomics and Stroke: Introduction Stroke, November 1, 2004; 35(11_suppl_1): 2731 - 2734. [Full Text] [PDF]
|
|
|
|
 |
|
 I. Bank, E. J. Libourel, S. Middeldorp, E. C. M. van Pampus, M. M. W. Koopman, K. Hamulyak, M. H. Prins, J. van der Meer, and H. R. Buller Prothrombin 20210A Mutation: A Mild Risk Factor for Venous Thromboembolism but Not for Arterial Thrombotic Disease and Pregnancy-Related Complications in a Family Study Arch Intern Med, September 27, 2004; 164(17): 1932 - 1937. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Albers, P. Amarenco, J. D. Easton, R. L. Sacco, and P. Teal Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 483S - 512S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z Szolnoki, F Somogyvari, A Kondacs, M Szabo, L Fodor, J Bene, and B Melegh Evaluation of the modifying effects of unfavourable genotypes on classical clinical risk factors for ischaemic stroke J. Neurol. Neurosurg. Psychiatry, December 1, 2003; 74(12): 1615 - 1620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Donahue, D. Gailani, M. S. Higgins, D. C. Drinkwater, and A. L. George Jr Factor V Leiden Protects Against Blood Loss and Transfusion After Cardiac Surgery Circulation, February 25, 2003; 107(7): 1003 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Austin, M. I. Chimowitz, H. A. Hill, S. Chaturvedi, L. R. Wechsler, R. J. Wityk, E. Walz, J. L. Wilterdink, B. Coull, C. A. Sila, et al. Cryptogenic Stroke in Relation to Genetic Variation in Clotting Factors and Other Genetic Polymorphisms Among Young Men and Women * Editorial Comment Stroke, December 1, 2002; 33(12): 2762 - 2768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Juul, A. Tybjarg-Hansen, R. Steffensen, S. Kofoed, G. Jensen, and B. G. Nordestgaard Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses Blood, June 17, 2002; 100(1): 3 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Madonna, V. de Stefano, A. Coppola, F. Cirillo, A. M. Cerbone, G. Orefice, and G. Di Minno Hyperhomocysteinemia and Other Inherited Prothrombotic Conditions in Young Adults With a History of Ischemic Stroke Stroke, January 1, 2002; 33(1): 51 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Herrington and K. P. Klein Genome and Hormones: Gender Differences in Physiology: Invited Review: Pharmacogenetics of estrogen replacement therapy J Appl Physiol, December 1, 2001; 91(6): 2776 - 2784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Strater, K. Kurnik, C. Heller, R. Schobess, P. Luigs, and U. Nowak-Gottl Aspirin Versus Low-Dose Low-Molecular-Weight Heparin: Antithrombotic Therapy in Pediatric Ischemic Stroke Patients: A Prospective Follow-Up Study Stroke, November 1, 2001; 32(11): 2554 - 2558. [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]
|
|
|
|
|
|
G. J. Hankey, J. W. Eikelboom, F. M. van Bockxmeer, E. Lofthouse, N. Staples, and R. I. Baker Inherited Thrombophilia in Ischemic Stroke and Its Pathogenic Subtypes Stroke, August 1, 2001; 32(8): 1793 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mira, J. Todoli, R. Alonso, M. L. Mico, A. Vaya, F. Ferrando, A. Estelles, P. Villa, and J. Aznar Factor V Leiden and Prothrombin G20210A in Relation to Arterial and/or Vein Rethrombosis: Two Cases Clinical and Applied Thrombosis/Hemostasis, July 1, 2001; 7(3): 234 - 237. [Abstract] [PDF]
|
|
|
|
|
|
C. Russo, D. Girelli, O. Olivieri, P. Guarini, F. Manzato, F. Pizzolo, B. Zaia, A. Mazzucco, and R. Corrocher G20210A Prothrombin Gene Polymorphism and Prothrombin Activity in Subjects With or Without Angiographically Documented Coronary Artery Disease Circulation, May 22, 2001; 103(20): 2436 - 2440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Kamigaki, D. S. Siscovick, S. M. Schwartz, B. M. Psaty, K. L. Edwards, T. E. Raghunathan, and M. A. Austin Low Density Lipoprotein Particle Size and Risk of Early-Onset Myocardial Infarction in Women Am. J. Epidemiol., May 15, 2001; 153(10): 939 - 945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Kamphuisen, J. C. J. Eikenboom, and R. M. Bertina Elevated Factor VIII Levels and the Risk of Thrombosis Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 731 - 738. [Full Text] [PDF]
|
|
|
|
|
|
G.J. Hademenos, M.J. Alberts, I. Awad, M. Mayberg, T. Shephard, A. Jagoda, R.E. Latchaw, H.W. Todd, K. Viste, R. Starke, et al. Advances in the genetics of cerebrovascular disease and stroke Neurology, April 24, 2001; 56(8): 997 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Federman and R. S. Kirsner An Update on Hypercoagulable Disorders Arch Intern Med, April 23, 2001; 161(8): 1051 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Frank, A. P. Reiner, S. M. Schwartz, P. N. Kumar, R. M. Pearce, P. G. Arbogast, W. T. Longstreth Jr, F. R. Rosendaal, B. M. Psaty, and D. S. Siscovick The Kozak sequence polymorphism of platelet glycoprotein Ib{alpha} and risk of nonfatal myocardial infarction and nonfatal stroke in young women Blood, February 15, 2001; 97(4): 875 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O C BACKHOUSE, M J MENAGE, and B A McVERRY Familial thrombophilia and normal tension glaucoma Br J Ophthalmol, January 1, 2001; 85(1): 110j - 110. [Full Text]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
C. D. Bushnell and L. B. Goldstein Diagnostic Testing for Coagulopathies in Patients With Ischemic Stroke Stroke, December 1, 2000; 31(12): 3067 - 3078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hassan and H. S. Markus Genetics and ischaemic stroke Brain, September 1, 2000; 123(9): 1784 - 1812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. Reiner, P. N. Kumar, S. M. Schwartz, W. T. Longstreth Jr, R. M. Pearce, F. R. Rosendaal, B. M. Psaty, and D. S. Siscovick Genetic Variants of Platelet Glycoprotein Receptors and Risk of Stroke in Young Women Stroke, July 1, 2000; 31(7): 1628 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Madonna, V. De Stefano, A. Coppola, R. Albisinni, and A. M. Cerbone G20210A PRTH Gene Mutation and Other Trombophilic Polymorphisms in Patients With Cerebral Vein Thrombosis Stroke, July 1, 2000; 31 (7): 1785 - 1790. [Full Text] [PDF]
|
|
|
|
|
|
F. J. Kirkham, M. Prengler, D. K.M. Hewes, and V. Ganesan Risk Factors for Arterial Ischemic Stroke in Children J Child Neurol, May 1, 2000; 15(5): 299 - 307. [Abstract] [PDF]
|
|
|
|
|
|
M. J. Kupferminc, D. Yair, N. M. Bornstein, J. B. Lessing, and A. Eldor Transient Focal Neurological Deficits During Pregnancy in Carriers of Inherited Thrombophilia Stroke, April 1, 2000; 31(4): 892 - 895. [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]
|
|
|
|
|
|
U. Nowak-Gottl, R. Strater, A. Heinecke, R. Junker, H.-G. Koch, G. Schuierer, and A. von Eckardstein Lipoprotein (a) and Genetic Polymorphisms of Clotting Factor V, Prothrombin, and Methylenetetrahydrofolate Reductase Are Risk Factors of Spontaneous Ischemic Stroke in Childhood Blood, December 1, 1999; 94(11): 3678 - 3682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Redondo, H. H. Watzke, B. Stucki, I. Sulzer, F. D. Biasiutti, B. R. Binder, M. Furlan, B. Lammle, and W. A. Wuillemin Coagulation Factors II, V, VII, and X, Prothrombin Gene 20210G->A Transition, and Factor V Leiden in Coronary Artery Disease : High Factor V Clotting Activity Is an Independent Risk Factor for Myocardial Infarction Arterioscler Thromb Vasc Biol, April 1, 1999; 19(4): 1020 - 1025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Ridker, C. H. Hennekens, and J. P. Miletich G20210A Mutation in Prothrombin Gene and Risk of Myocardial Infarction, Stroke, and Venous Thrombosis in a Large Cohort of US Men Circulation, March 2, 1999; 99(8): 999 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J HAAN, G G SCHOONMAN, G M TERWINDT, M D FERRARI, R M BERTINA, L J KAPPELLE, and J HAAN Prothrombotic mutations and ischaemic stroke at a young age in two sisters J. Neurol. Neurosurg. Psychiatry, December 1, 1998; 65(6): 958 - 959. [Full Text]
|
|