ISGS: The Ischemic Stroke Genetics Study

Project: Research project

Project Details


DESCRIPTION (provided by applicant): Stroke is the third leading cause of death
in industrialized countries and the leading cause of disability in adults.
Epidemiological and twins studies strongly support an inherited component to
stroke risk. The broad long-term objective of this application is to clarify
the molecular basis for inherited ischemic stroke risk. The application focuses
on thrombosis genes because of overwhelming evidence for the etiologic
relevance of thrombosis in acute ischemic stroke that comes from clinical
prevention and treatment trials and emergent angiography studies. The specific
aims of this application are: (1) to collect DNA and create immortalized cell
lines from patients with recent ischemic stroke and from healthy control
subjects and (2) to test for associations between ischemic stroke and candidate
thrombosis genes. The candidate genes to be tested are the beta fibrinogen gene
and genes that code for components of 3 platelet glycoprotein receptors
GPIIb/IIIa, GPIb, and GPla. These genes were selected based on previous studies
demonstrating associations between variations in these genes and ischemic
stroke, either overall or in subgroup analyses. Four hundred and fifty [450]
patients with recent CTIMR-confirmed ischemic stroke will be recruited from
inpatient services at 5 US clinical centers over 3 years. Four hundred and
fifty [450] controls will be enrolled concurrently. Matching criteria will be
age, sex, and race (African-American versus non-African-American). The
prospective design of this application permits rigorous exploration of whether
there is heterogeneity in genetic risk factors among common ischemic stroke
subtypes that are defined clinically. Patients will have dual subtyping by
certified study neurologists using standardized classification systems: the
Trial of ORG 10172 Acute Stroke Treatment (TOAST) system and the Oxfordshire
Community Stroke Project system. This application has been designed to permit
valid pooled analyses with SWISS, an ongoing affected sibling pair study
supported by the NINDS (ROI NS39987). The application and SWISS share the same
definitions for the present and absence of phenotype and key enrollment
StatusNot started


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