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

Abstract

Background: Post-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 ϵ4) 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. Objective: Examine the influence of genetic polymorphism on post-stroke UL motor improvement. Design: Systematic Review and Meta-Analysis Methods: We 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 to0.18), medium (0.19 to 0.40) and large (≥0.41). Results: We 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 to 0.88) and at retention (0.58, 95% CI: 0.06 to 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. Conclusion: BDNF val66met and COMT val158met polymorphisms negatively influence UL motor improvement in impairment and activity scores. Registration: https://osf.io/wk9cf/

Competing Interest Statement

The authors have declared no competing interest.

Clinical Protocols

https://osf.io/wk9cf/

Funding Statement

The study was funded by a Pilot grant from the Center for Biomedical Neurosciences, UT Health San Antonio

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The data were obtained from studies used in the systematic review and meta-analysis. Only published data were used for the analysis

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Data Availability

All data produced in the present work are contained in the manuscript

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