Advancing Stroke Therapeutics Through Genetic Understanding

Stroke is a complex neurological disorder that most likely results from an intricate interplay between lifestyle, environment and genetics. Genes can influence susceptibility to stroke, alter responses to pharmacotherapy, and affect disease outcome. Recently, common variations within the PDE4D and ALOX5AP genes have been identified that increase population-attributable risk of stroke in Iceland. These genes are yet to be unequivocally confirmed and the functional variants identified. Characterizing the genetic profile of individuals at highest risk of stroke will permit more targeted pharmacological approaches to early primary and secondary stroke prevention. Pharmacogenomics is likely to be particularly important for stroke prevention because of the narrow therapeutic index for treatments like warfarin that prevents thrombosis but also promotes hemorrhage. Identifying possible genetic determinants of outcome will also open new avenues of research into stroke therapeutics beyond thrombolysis.