Association between genetic variation in the dopamine system and motor recovery after stroke

Article type: Research Article

Authors: Kim, Bo-Ram^a | Kim, Hahn Young^b | Chun, Young Il^c | Yun, Yeo-Min^d | Kim, Hyuntae^a | Choi, Dong-Hee^{e; f} | Lee, Jongmin^{a; f; *}

Affiliations: [a] Department of Rehabilitation Medicine, Konkuk University School of Medicine and Medical Center, Seoul, Korea | [b] Department of Neurology, Konkuk University School of Medicine and Medical Center, Seoul, Korea | [c] Department of Neurosurgery, Konkuk University School of Medicine and Medical Center, Seoul, Korea | [d] Department of Laboratory Medicine, Konkuk University School of Medicine and Medical Center, Seoul, Korea | [e] Department of Medical Science, Konkuk University School of Medicine, Seoul, Korea | [f] Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul, Korea

Correspondence: [*] Corresponding author: Jongmin Lee, Department of Rehabilitation Medicine, Konkuk University Medical Center, 120-1, Neungdong-ro, Gwangjin-Gu, Seoul 05030, Korea. Tel.: +82 2 2030 5345; Fax: +82 2 2030 5379; E-mail: leej@kuh.ac.kr.

Abstract: Background: The dopamine system plays a key role in motor learning and neuroplasticity. Several studies have studied the efficacy of dopaminergic drugs in enhancing motor recovery after stroke, but the effects are controversial. Although genetic variations in plasticity-related genes influence each individual’s capacity for recovery after stroke, limited studies have investigated the effects of polymorphism of dopamine-related genes. Objective: We aimed to investigate the association between motor recovery in stroke patients and polymorphisms in the dopamine-related genes catechol-O-methyltransferase (COMT), dopamine receptor D1 (DRD1), DRD2, and DRD3. Methods: We enrolled 74 patients with first-ever stroke (42 males, 32 females, mean age: 61.4±14.1 y). During admission, blood samples were collected, and the genotypes of COMT, DRD1, DRD2, and DRD3 were analyzed. The primary outcome was assessed with Fugl-Meyer Assessment (FMA) at 1 week, 3 months, and 6 months after stroke; secondary outcomes were assessed with Functional Independence Measure (FIM) and mini-mental state examination at 3 and 6 months after stroke. The association between polymorphisms and functional outcome was analyzed. Results: There were no significant associations between COMT polymorphisms and FMA or FIM scores at 1 week after stroke or between DRD1, DRD2, or DRD3 genotypes and FMA or FIM scores at any point. COMT genotypes were significantly associated with FMA and FIM at 3 months (p < 0.01 and p < 0.05, respectively) and at 6 months (p < 0.01 and p < 0.05, respectively). Conclusion: These data suggest that genetic variation of dopamine-related genes may affect motor recovery after stroke and that COMT polymorphism could be useful for predicting motor recovery.

Keywords: Stroke, single-nucleotide polymorphism, dopamine, rehabilitation

DOI: 10.3233/RNN-160667

Journal: Restorative Neurology and Neuroscience, vol. 34, no. 6, pp. 925-934, 2016