The pathogenesis of ischemic stroke remains unknown but a better
knowledge of its pathogenetic mechanism may help us in identifying more effective
therapies to reduce the the disease burden. Family and twin studies support the role of
genetic factors in stroke pathophysiology. A number of monogenic conditions
presenting with stroke have been described. They account for only a small proportion
of strokes, but it is believed they are underestimated and the study of these diseases
may provide insight in the pathogenic pathways of stroke, given also the existence of
animal models in which examine disease mechanisms. However, in most cases, stroke
is believed to be a multifactorial disorder. A number of genetic association studies
using the candidate gene approach have failed in demonstrating reliable associations
between stroke and genetic variants. Although several molecular variants resulted from
GWAS strongly associated with ischemic stroke risk, they account for only a small part
of the risk of ischemic stroke. Moreover, the pathogenic significance of many of these
genetic variants has yet to be determined by functional studies so that the significance
of these findings in clinical practice has been limited. Interestingly, the studies
conducted so far demonstrated that the majority of the identified genetic variants found
were associated with specific stroke subtypes, supporting the hypothesis that distinct
genetic architecture and pathophysiological mechanisms underlie specific stroke
subtypes.
