Cryptogenic stroke in relation to genetic variation in clotting factors and other genetic polymorphisms among young men and women

Harland Austin, Marc I. Chimowitz, Holly A. Hill, Seemant Chaturvedi, Lawrence R. Wechsler, Robert J. Wityk, Elizabeth Walz, Janet L. Wilterdink, Bruce Coull, Cathy A. Sila, Panos Mitsias, Bruce Evatt, W. Craig Hooper

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Background and Purpose - The purpose of the present study was to compare the prevalences of genetic polymorphisms in persons with cryptogenic stroke with those among stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke). Methods - We compared the prevalences of genetic polymorphisms thought to be related to thrombi formation in young stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke; controls; n=79) with those in young stroke patients without such sources (cryptogenic stroke; cases; n=67). Common variations in the genes encoding factor V, prothrombin, angiotensin 1-converting enzyme, 5,10-methylene-tetrahydrofolate reductase, endothelial cell nitric oxide synthase, tissue plasminogen activator, plasminogen activator inhibitor-1, and fibrinogen were evaluated. We also compared the allele prevalence of these genes among all stroke patients with those among a large pool of historical controls assayed for these genes. Results - None of these genetic polymorphisms was statistically significantly related to cryptogenic stroke. With respect to a comparison of all ischemic stroke with historical controls, only the prevalence of tissue plasminogen activator D allele among stroke subjects was statistically significantly higher than that of the historical controls (P=0.0014). Conclusions-These findings generally do not support the hypothesis that genes associated with a prothrombotic state are risk factors among a subgroup of young people with stroke of undetermined cause. Except for the D tissue plasminogen activator allele, the findings also indicated that these genetic factors are unrelated, or only weakly related, to all ischemic stroke.

Original languageEnglish (US)
Pages (from-to)2762-2768
Number of pages7
JournalStroke
Volume33
Issue number12
DOIs
StatePublished - Dec 1 2002
Externally publishedYes

Fingerprint

Blood Coagulation Factors
Genetic Polymorphisms
Stroke
Tissue Plasminogen Activator
Alleles
Genes
Arteries
Methylenetetrahydrofolate Reductase (NADPH2)
Factor V
Nitric Oxide Synthase Type III
Plasminogen Activator Inhibitor 1
Prothrombin
Peptidyl-Dipeptidase A
Fibrinogen
Thrombosis
Endothelial Cells

Keywords

  • Coagulation
  • Factor V
  • Genetics
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Cryptogenic stroke in relation to genetic variation in clotting factors and other genetic polymorphisms among young men and women. / Austin, Harland; Chimowitz, Marc I.; Hill, Holly A.; Chaturvedi, Seemant; Wechsler, Lawrence R.; Wityk, Robert J.; Walz, Elizabeth; Wilterdink, Janet L.; Coull, Bruce; Sila, Cathy A.; Mitsias, Panos; Evatt, Bruce; Craig Hooper, W.

In: Stroke, Vol. 33, No. 12, 01.12.2002, p. 2762-2768.

Research output: Contribution to journalArticle

Austin, H, Chimowitz, MI, Hill, HA, Chaturvedi, S, Wechsler, LR, Wityk, RJ, Walz, E, Wilterdink, JL, Coull, B, Sila, CA, Mitsias, P, Evatt, B & Craig Hooper, W 2002, 'Cryptogenic stroke in relation to genetic variation in clotting factors and other genetic polymorphisms among young men and women', Stroke, vol. 33, no. 12, pp. 2762-2768. https://doi.org/10.1161/01.STR.0000038094.79901.3B
Austin, Harland ; Chimowitz, Marc I. ; Hill, Holly A. ; Chaturvedi, Seemant ; Wechsler, Lawrence R. ; Wityk, Robert J. ; Walz, Elizabeth ; Wilterdink, Janet L. ; Coull, Bruce ; Sila, Cathy A. ; Mitsias, Panos ; Evatt, Bruce ; Craig Hooper, W. / Cryptogenic stroke in relation to genetic variation in clotting factors and other genetic polymorphisms among young men and women. In: Stroke. 2002 ; Vol. 33, No. 12. pp. 2762-2768.
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AU - Austin, Harland

AU - Chimowitz, Marc I.

AU - Hill, Holly A.

AU - Chaturvedi, Seemant

AU - Wechsler, Lawrence R.

AU - Wityk, Robert J.

AU - Walz, Elizabeth

AU - Wilterdink, Janet L.

AU - Coull, Bruce

AU - Sila, Cathy A.

AU - Mitsias, Panos

AU - Evatt, Bruce

AU - Craig Hooper, W.

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N2 - Background and Purpose - The purpose of the present study was to compare the prevalences of genetic polymorphisms in persons with cryptogenic stroke with those among stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke). Methods - We compared the prevalences of genetic polymorphisms thought to be related to thrombi formation in young stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke; controls; n=79) with those in young stroke patients without such sources (cryptogenic stroke; cases; n=67). Common variations in the genes encoding factor V, prothrombin, angiotensin 1-converting enzyme, 5,10-methylene-tetrahydrofolate reductase, endothelial cell nitric oxide synthase, tissue plasminogen activator, plasminogen activator inhibitor-1, and fibrinogen were evaluated. We also compared the allele prevalence of these genes among all stroke patients with those among a large pool of historical controls assayed for these genes. Results - None of these genetic polymorphisms was statistically significantly related to cryptogenic stroke. With respect to a comparison of all ischemic stroke with historical controls, only the prevalence of tissue plasminogen activator D allele among stroke subjects was statistically significantly higher than that of the historical controls (P=0.0014). Conclusions-These findings generally do not support the hypothesis that genes associated with a prothrombotic state are risk factors among a subgroup of young people with stroke of undetermined cause. Except for the D tissue plasminogen activator allele, the findings also indicated that these genetic factors are unrelated, or only weakly related, to all ischemic stroke.

AB - Background and Purpose - The purpose of the present study was to compare the prevalences of genetic polymorphisms in persons with cryptogenic stroke with those among stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke). Methods - We compared the prevalences of genetic polymorphisms thought to be related to thrombi formation in young stroke patients with evidence of large-artery occlusive disease or an unequivocal cardioembolic source (noncryptogenic stroke; controls; n=79) with those in young stroke patients without such sources (cryptogenic stroke; cases; n=67). Common variations in the genes encoding factor V, prothrombin, angiotensin 1-converting enzyme, 5,10-methylene-tetrahydrofolate reductase, endothelial cell nitric oxide synthase, tissue plasminogen activator, plasminogen activator inhibitor-1, and fibrinogen were evaluated. We also compared the allele prevalence of these genes among all stroke patients with those among a large pool of historical controls assayed for these genes. Results - None of these genetic polymorphisms was statistically significantly related to cryptogenic stroke. With respect to a comparison of all ischemic stroke with historical controls, only the prevalence of tissue plasminogen activator D allele among stroke subjects was statistically significantly higher than that of the historical controls (P=0.0014). Conclusions-These findings generally do not support the hypothesis that genes associated with a prothrombotic state are risk factors among a subgroup of young people with stroke of undetermined cause. Except for the D tissue plasminogen activator allele, the findings also indicated that these genetic factors are unrelated, or only weakly related, to all ischemic stroke.

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KW - Factor V

KW - Genetics

KW - Stroke

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