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.
Ross
O A
OA
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Worrall
B B
BB
Meschia
J F
JF
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000235:genetics; D058927:5-Lipoxygenase-Activating Proteins; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002545:Brain Ischemia / Q000150:complications* / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002543:Cerebral Hemorrhage / Q000150:complications / Q000235:genetics; D017281:Cost of Illness; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D018579:Patient Selection; D010597:Pharmacogenetics; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000235:genetics* / Q000517:prevention & control*; D016896:Treatment Outcome
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D005343:Fibrinolytic Agents; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human