Genetic Polymorphisms and Post-Stroke Upper Limb Motor Improvement – A Systematic Review and Meta-Analysis

AbstractBackgroundPost-stroke upper limb (UL) motor improvement is associated with adaptive neuroplasticity and motor learning. Both intervention-related (including provision of intensive, variable, and task-specific practice) and individual-specific factors (including the presence of genetic polymorphisms) influence improvement. In individuals with stroke, most commonly, polymorphisms are found in Brain Derived Neurotrophic Factor (BDNF), Apolipoprotein (APOE) and catechol-O-methyltransferase (COMT). These involve a replacement of cystine by arginine (APOEε4) or one or two valines by methionine (BDNF: val66met, COMT: val158met). However, the implications of these polymorphisms on post-stroke UL motor improvement specifically have not yet been elucidated.ObjectiveExamine the influence of genetic polymorphism on post-stroke UL motor improvement.DesignSystematic Review and Meta-AnalysisMethodsWe conducted a systematic search of the published literature in English language of using standard methodology. The modified Downs and Black checklist helped assess study quality. We compared change in UL motor impairment and activity scores between individuals with and without the polymorphisms. Meta-analyses helped assess change in motor impairment scores based upon a minimum of two studies per time point. Effect sizes (ES) were quantified based upon the Rehabilitation Treatment Specification System as follows: small (0.08–0.18), medium (0.19–0.40) and large (≥0.41).ResultsWe retrieved 10 (four good and six fair quality) studies. Compared to those with BDNF val66met polymorphism, meta-analyses revealed lower motor impairment scores (large ES) in those without the polymorphism at intervention completion (0.5, 95% CI: 0.11-0.88) and at retention (0.58, 95% CI: 0.06-1.11). Presence of CoMT val158met polymorphism had similar results, with higher levels of improvement in impairment (large ES ≥1.5) and activity scores (large ES ranging from 0.5-0.76) in those without the polymorphism. Presence of APOEε4 form did not influence UL motor improvement.ConclusionBDNF val66met and COMT val158met polymorphisms negatively influence UL motor improvement in impairment and activity scores.Registrationhttps://osf.io/wk9cf/