Investigation of candidate genes and other major clinical and demographic risk factors for stroke - the Australian Stroke Genetics Collaborative

Background:

Recent animal, twin, family and case control studies provide strong evidence supporting a polygenic predisposition to ischemic stroke. The magnitude of this predisposition varies according to stroke subtype, with the greatest risk associated with lacunar and atherothromboembolic stroke.

The candidate gene approach is a method used to investigate the genetic predisposition of ischemic stroke. It relies on determining an association between ischaemic stroke and known genetic single nucleotide polymorphisms (SNPs) of functional significance. A prospective case-control study design is commonly used to compare the prevalence of a SNP between ischaemic stroke cases and a normal control group. Candidate SNPs are chosen based on their influence on genes underlying the pathological process.

In ischaemic stroke, genes influencing atherosclerosis, platelet function, coagulation and fibrinolysis are plausible candidates for investigation, based on known pathogenic models. Although biological plausibility is essential in the selection of candidate genes, other methodological issues such as sample size estimation and ethnic allelic variation also require consideration prior to candidate gene selection.

Project Description:

The primary aim of this clinical research is to identify SNPs and other clinical and demographic risk factors that play an important role in the pathogenesis of and predisposition to ischemic stroke.  The Neurogenetics Laboratory of the Stroke Research Programme in the Basil Hetzel Institute at The Queen Elizabeth Hospital has joined a national collaborative of multiple centres to investigate genotyping and risk factor analysis in stroke.  Our own population study of 182 patients with acute ischemic stroke and 301 non-hospitalised controls has contributed. 

Patients are still being collected and are evaluated for known cerebrovascular risk factors and classified for stroke subtype.  A cerebrovascular risk factor profile is also determined and SNP genotypes are determined using polymerase chain reaction (PCR) methods. 

Programme coordinators:  Dr Jim Jannes,  A/Prof. Simon Koblar