The Ischemic Stroke Genetics Study (ISGS) Protocol.
BACKGROUND
The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype.


METHODS
The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes beta-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future.


CONCLUSIONS
The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes.
Meschia
James F
JF
Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA. Meschia.James@mayo.edu
Brott
Thomas G
TG
Brown
Robert D
RD
Crook
Richard J P
RJ
Frankel
Michael
M
Hardy
John
J
Merino
José G
JG
Rich
Stephen S
SS
Silliman
Scott
S
Worrall
Bradford Burke
BB
D000046:Academic Medical Centers; D000328:Adult; D002545:Brain Ischemia / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D002985:Clinical Protocols; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D010980:Platelet Membrane Glycoproteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D012016:Reference Values; D018401:Sample Size; D020521:Stroke / Q000150:complications / Q000235:genetics*; D014481:United States
D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen