Genetic risk factors for stroke: insights into pathophysiology from candidate gene approaches

Ischaemic stroke and haemorrhagic stroke are believed to result from both shared and different determinants, and thus the genetic variants that influence these clinical endpoints are likely to differ. Studies involving twins, siblings, and families have detected significant evidence for heritability, but to date, the identification of the genes involved is unclear. Study of the genetic determinants of some of the underlying traits known to contribute to risk of stroke may be fruitful. Of these, carotid Intimal–Medial wall Thickness (IMT) is particularly relevant, since it is a surrogate measure of subclinical atherosclerosis and is a strong predictor of future stroke. Some studies have reported that IMT is higher among subjects carrying functional variants in genes related to matrix deposition (stromelysin-1), inflammation (interleukin-6), and lipid metabolism (hepatic lipase, ApoE, CETP, and PON1). The published data will be reviewed to determine the robustness of these associations.