ABSTRACT NUMBER: ESOC2026A1611 GENETIC DETERMINANTS OF POST-STROKE OUTCOMES: A NARRATIVE REVIEW OF BDNF, APOE, ACE, AND MONOAMINERGIC GENES

Abstract Background and aims Stroke remains a leading cause of death and disability worldwide. Substantial variability exists in post-stroke recovery outcomes, with accumulating evidence suggesting that genetic polymorphisms play an important role in determining recovery trajectories through their effects on neuroplasticity and neural repair mechanisms. This narrative review examines the associations between well-characterized genetic polymorphisms and post-stroke outcomes, focusing on their influence on recovery across multiple domains. Methods Literature was synthesized on five extensively studied gene categories: brain-derived neurotrophic factor (BDNF), apolipoprotein E (APOE), angiotensin-converting enzyme (ACE), serotonin-related genes, and dopaminergic genes. Evidence was reviewed regarding their associations with global functional, motor, emotional, and cognitive outcomes after stroke. Results The BDNF Val66Met polymorphism demonstrates associations with motor cortical plasticity and motor outcomes, with the Met allele generally linked to reduced experience-dependent plasticity, though intensive rehabilitation may overcome these effects. APOE ε4 shows consistent associations with cognitive decline and emotional outcomes, while effects on motor and functional recovery vary by stroke subtype. ACE gene polymorphisms, particularly rs4291 and the insertion/deletion variant, influence emotional outcomes and functional recovery through neurohormonal mechanisms. The serotonin transporter 5-HTTLPR polymorphism demonstrates associations with emotional vulnerability and depression susceptibility. Dopaminergic system polymorphisms, including COMT Val158Met, show associations with motor outcomes and cognitive performance. Conclusions Genetic polymorphisms represent important biological determinants of stroke recovery. However, effect sizes are generally modest, replication studies show inconsistency, and outcome measures vary widely. Larger multicenter studies with standardized methodologies are needed to advance understanding and enable potential clinical applications in personalized stroke rehabilitation. Conflict of interest Prach Uthayo: nothing to disclose