Genetic variation in the vesicular monoamine transporter

Preliminary associations with cognitive outcomes after severe traumatic brain injury

Steven M. Markos, Michelle D. Failla, Anne C. Ritter, C. Edward Dixon, Yvette P. Conley, Joseph H. Ricker, Patricia M. Arenth, Shannon B. Juengst, Amy K. Wagner

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E24-E34
JournalJournal of Head Trauma Rehabilitation
Volume32
Issue number2
DOIs
StatePublished - Jan 1 2017

Fingerprint

Vesicular Monoamine Transport Proteins
Cognition
Homozygote
Synaptic Transmission
Genes
Single Nucleotide Polymorphism
Traumatic Brain Injury
Multivariate Analysis
Genotype

Keywords

  • Cognition
  • Depression
  • Genetic polymorphism
  • Rehabilomics
  • Traumatic brain injury
  • Vesicular monoamine transporter type 2 (VMAT2)

ASJC Scopus subject areas

  • Physical Therapy, Sports Therapy and Rehabilitation
  • Rehabilitation
  • Clinical Neurology

Cite this

Genetic variation in the vesicular monoamine transporter : Preliminary associations with cognitive outcomes after severe traumatic brain injury. / Markos, Steven M.; Failla, Michelle D.; Ritter, Anne C.; Dixon, C. Edward; Conley, Yvette P.; Ricker, Joseph H.; Arenth, Patricia M.; Juengst, Shannon B.; Wagner, Amy K.

In: Journal of Head Trauma Rehabilitation, Vol. 32, No. 2, 01.01.2017, p. E24-E34.

Research output: Contribution to journalArticle

Markos, Steven M. ; Failla, Michelle D. ; Ritter, Anne C. ; Dixon, C. Edward ; Conley, Yvette P. ; Ricker, Joseph H. ; Arenth, Patricia M. ; Juengst, Shannon B. ; Wagner, Amy K. / Genetic variation in the vesicular monoamine transporter : Preliminary associations with cognitive outcomes after severe traumatic brain injury. In: Journal of Head Trauma Rehabilitation. 2017 ; Vol. 32, No. 2. pp. E24-E34.
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