Genetic polymorphisms and post-stroke upper limb motor improvement - A systematic review and meta-analysis

BackgroundPost-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 (APOE epsilon 4) or valines by 1 or 2 methionines (BDNF:val66met, met66met; COMT:val158met; met158met). 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-Analysis.MethodsWe conducted a systematic search of the literature published in English language. 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 (Fugl Meyer Assessment) scores based upon a minimum of 2 studies/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 (4 good and 6 fair quality) studies. Compared to those with BDNF val66met and met66met polymorphism, meta-analyses revealed lower motor impairment (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). The presence of CoMT val158met or met158met polymorphism had similar results, with lower impairment (large ES >= 1.5) and higher activity scores (large ES ranging from 0.5-0.76) in those without the polymorphism. Presence of APOE epsilon 4 form did not influence UL motor improvement.ConclusionPolymorphisms with the presence of 1 or 2 met alleles in BDNF and COMT negatively influence UL motor improvement.Registrationhttps://osf.io/wk9cf/. This research paper focuses on the impact of variations in DNA sequence in certain genes on improvement seen in the arms in people who have had a stroke. In this study, we studied the role of 3 genes previously identified as having variations in DNA sequence. The authors searched published research articles from 2000 onwards and selected articles that satisfied certain criteria. We then checked the quality of the selected papers. Next, we combined common data from same tests used to examine motor improvement in the arms to check if there was an overall effect. A total of 10 papers were found. The selected articles were either good or moderate in quality. Variations in DNA structure in 2 out of the 3 genes studied affected the ability to improve the use of the arms in daily life after a stroke. Such information can have important implications in the extent of recovery that is possible after a stroke. It can also be helpful to decide the best rehabilitation options that can be offered to help maximize their ability to use the arms after a stroke.