Genetic signatures in the treatment of stroke

Stroke is the fourth leading cause of mortality and neurological disability. It is caused by an intricate interplay of environmental and genetic factors. Genes not only influence susceptibility to stroke but have also been found to alter the response to pharmacological agents and may also influence the clinical outcome of the disease. Current treatment strategies for stroke include tissue plasminogen activator, antiplatelet agents and lipid lowering drugs. These act via diverse mechanisms of actions and are centered around the management of modifiable risk factors to prevent the recurrent stroke events. However, a significant number of patients experience poor clinical outcome due to recurrent stroke events and drug induced adverse reactions. Therefore, accurate risk management and targeted prevention strategies remain yet to be explored at the level of individual patients with stroke. Pharmacogenetic based research studies have identified the relation between genetic factors and inter-individual variability towards drug treatment. Several single nucleotide polymorphisms in genes encoding for metabolizers, transporters and target receptors have been reported to influence the pharmacokinetics and pharmacodynamics of drugs used in the treatment of stroke. Many candidate gene studies have investigated the role of genetic variants in association with altered drug response in stroke treatment. However, these results are limited to clinical trials and should be replicated in Genome Wide Association (GWAS) Studies. In addition to this long term follow up prospective studies would be helpful in predicting drug induced risk/benefit ratio. Pharmacogenetic studies will reveal the correlation between variation in drug responses on the basis of the individual's genomic profile better known as Personalized or Individualized Medicines. This will also optimize risk assessment and will stratify the population requiring careful attention before prescribing a particular medicine to achieve maximum therapeutic benefit. Moreover, this will help in designing the novel therapeutic agents with a targeted approach. In this concern, the Genomics and Randomized Trials Network (GARNET) has been created, which is a Pharmacogenomics Consortium aimed to identify genetic variants affecting an individual's response to treatment with the help of advanced technology. This review will address the major issues of therapeutic failures concerned with existing drugs used in the treatment of stroke and the need for exploring new and targeted therapeutic strategies based on pharmacogenetics.