Published online before print April 24, 2003, doi: 10.1161/01.STR.0000069723.17984.FD
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2003;34:1364.)
© 2003 American Heart Association, Inc.
Original Contributions |
Evaluating the Genetic Component of Ischemic Stroke Subtypes
A Family History Study
From the Department of Clinical Neurosciences, St George’s Hospital Medical School, London, UK.
Correspondence to Dr Paula Jerrard-Dunne, Department of Clinical Neurosciences, St George’s Hospital Medical School, Cranmer Terrace, Tooting, London SW17 0RE, UK. E-mail pjerrard{at}sghms.ac.uk
Background and Purpose— Twin and family history studies support a role for genetic factors in stroke risk. Because the etiology of ischemic stroke is heterogeneous, genetic factors may vary by etiologic subtype. We determined the familial aggregation of stroke risk in different stroke phenotypes and used the results to model estimated sample size requirements for case-control studies.
Methods— One thousand consecutive white subjects with ischemic stroke and 800 white controls matched for age and sex were recruited. A first-degree family history of stroke and myocardial infarction was obtained by structured interview. Stroke subtype was determined with the use of modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria.
Results— A family history of stroke at 
65 years was a significant risk factor for large-vessel disease (odds ratio [OR], 2.24; 95% CI, 1.49 to 3.36; P<0.001) and for small-vessel disease (OR, 1.93; 95% CI, 1.25 to 2.97; P=0.003). When only cases aged 65 years were considered, these ORs increased to 2.93 (95% CI, 1.68 to 5.13) (P<0.001) and 3.15 (95% CI, 1.81 to 5.50) (P<0.001), respectively. No significant associations were seen for cardioembolic stroke or stroke of undetermined etiology.
Conclusions— A family history of vascular disease is an independent risk factor for both large-vessel atherosclerosis and small-vessel disease, especially in cases presenting before age 65 years. The estimated sample sizes for case-control studies illustrate how candidate gene studies for ischemic stroke might be made more effective by focusing on these specific phenotypes, in which the genetic component of the disease appears to be strongest.
Key Words: cerebral infarction • epidemiology • genetics • risk factors • stroke classification
This article has been cited by other articles:
 |
|
 |
|
  H. S. Markus Genes, endothelial function and cerebral small vessel disease in man Exp Physiol, January 1, 2008; 93(1): 121 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lee and M. Kong An Interactive Association of Common Sequence Variants in the Neuropeptide Y Gene With Susceptibility to Ischemic Stroke Stroke, October 1, 2007; 38(10): 2663 - 2669. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Lalouschek, G. Endler, M. Schillinger, K. Hsieh, W. Lang, S. Cheng, P. Bauer, O. Wagner, and C. Mannhalter Candidate Genetic Risk Factors of Stroke: Results of a Multilocus Genotyping Assay Clin. Chem., April 1, 2007; 53(4): 600 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Wiklund, W. M. Brown, T. G. Brott, B. Stegmayr, R. D. Brown Jr, S. Nilsson-Ardnor, J. A. Hardy, B. M. Kissela, A. Singleton, D. Holmberg, et al. Lack of aggregation of ischemic stroke subtypes within affected sibling pairs Neurology, February 6, 2007; 68(6): 427 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.J.E. van Rijn, A. J.C. Slooter, A. F.C. Schut, A. Isaacs, Y. S. Aulchenko, P. J.L.M. Snijders, L. J. Kappelle, J. C. van Swieten, B. A. Oostra, and C. M. van Duijn Familial aggregation, the PDE4D gene, and ischemic stroke in a genetically isolated population Neurology, October 25, 2005; 65(8): 1203 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dichgans and H. S. Markus Genetic Association Studies in Stroke: Methodological Issues and Proposed Standard Criteria Stroke, September 1, 2005; 36(9): 2027 - 2031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Lynch, C. J. Han, L. E. Nee, and K. B. Nelson Prothrombotic Factors in Children With Stroke or Porencephaly Pediatrics, August 1, 2005; 116(2): 447 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Gormley, S. Bevan, A. Hassan, and H. S. Markus Polymorphisms in Genes of the Endothelin System and Cerebral Small-Vessel Disease Stroke, August 1, 2005; 36(8): 1656 - 1660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Jood, C. Ladenvall, A. Rosengren, C. Blomstrand, and C. Jern Family History in Ischemic Stroke Before 70 Years of Age: The Sahlgrenska Academy Study on Ischemic Stroke Stroke, July 1, 2005; 36(7): 1383 - 1387. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Moskau, A. Golla, C. Grothe, M. Boes, C. Pohl, and T. Klockgether Heritability of Carotid Artery Atherosclerotic Lesions: An Ultrasound Study in 154 Families Stroke, January 1, 2005; 36(1): 5 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Meschia Clinically Translated Ischemic Stroke Genomics Stroke, November 1, 2004; 35(11_suppl_1): 2735 - 2739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Markus Genes for stroke J. Neurol. Neurosurg. Psychiatry, September 1, 2004; 75(9): 1229 - 1231. [Full Text] [PDF]
|
|
|
|
|
|
A. Slowik, T. Dziedzic, W. Turaj, J. Pera, L. Glodzik-Sobanska, P. Szermer, M. T. Malecki, D. A. Figlewicz, and A. Szczudlik A2 Alelle of GpIIIa Gene Is a Risk Factor for Stroke Caused by Large-Vessel Disease in Males Stroke, July 1, 2004; 35(7): 1589 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U.G.R. Schulz, E. Flossmann, and P.M. Rothwell Heritability of Ischemic Stroke in Relation to Age, Vascular Risk Factors, and Subtypes of Incident Stroke in Population-Based Studies Stroke, April 1, 2004; 35(4): 819 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Alberts Genetics of Cerebrovascular Disease Stroke, February 1, 2004; 35(2): 342 - 344. [Full Text] [PDF]
|
|
|
|
|
|
E. Flossmann, U. G.R. Schulz, and P. M. Rothwell Systematic Review of Methods and Results of Studies of the Genetic Epidemiology of Ischemic Stroke Stroke, January 1, 2004; 35(1): 212 - 227. [Abstract] [Full Text] [PDF]
|
|