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Published on: September 11, 2017
Genetic Variation in the Vesicular Monoamine Transporter: Preliminary Associations With Cognitive Outcomes After
Steven M Markos1, Michelle D Failla, Anne C Ritter
1Department of Physical Medicine and Rehabilitation, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania (Drs Markos, Failla, Ritter, Dixon, Arenth, Juengst, and Wagner); Department of Neuroscience, University of Pittsburgh, Pittsburgh Pennsylvania (Dr Wagner); Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania (Drs Dixon and Wagner); Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania (Drs Dixon and Wagner); Pittsburgh VA Healthcare System, and Department of Neurological Surgery, School of Medicine, University of Pittsburgh (Dr Dixon); Department of Rehabilitation Medicine, New York University, School of Medicine, New York, New York (Dr Ricker); and Department of Human Genetics, University of Pittsburgh, School of Public Health, and Health Promotion and Development, University of Pittsburgh, School of Nursing, Pittsburgh, Pennsylvania (Dr Conley).
Introduction:
Traumatic brain injury (TBI) frequently results in impaired cognition, a function that can be modulated by monoaminergic signaling. Genetic variation among monoaminergic genes may affect post-TBI cognitive performance. The vesicular monoamine transporter-2 (VMAT2) gene may be a novel source of genetic variation important for cognitive outcomes post-TBI given VMAT2's role in monoaminergic neurotransmission.
Objective:
To evaluate associations between VMAT2 variability and cognitive outcomes post-TBI.
Methods:
We evaluated 136 white adults with severe TBI for variation in VMAT2 using a tagging single nucleotide polymorphism (tSNP) approach (rs363223, rs363226, rs363251, and rs363341). We show genetic variation interacts with assessed cognitive impairment (cognitive composite [Comp-Cog] T-scores) to influence functional cognition (functional independence measure cognitive [FIM-Cog] subscale] 6 and 12 months postinjury.
Results:
Multivariate analyses at 6 months postinjury showed rs363226 genotype was associated with Comp-Cog (P = .040) and interacted with Comp-Cog to influence functional cognition (P < .001). G-homozygotes had the largest cognitive impairment, and their cognitive impairment had the greatest adverse effect on functional cognition.
Discussion:
We provide the first evidence that genetic variation within VMAT2 is associated with cognitive outcomes after TBI. Further work is needed to validate this finding and elucidate mechanisms by which genetic variation affects monoaminergic signaling, mediating differences in cognitive outcomes.
