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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.
Afiliação
  • Markos SM; Department 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); Pitt
J Head Trauma Rehabil ; 32(2): E24-E34, 2017.
Article em En | MEDLINE | ID: mdl-26828714
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Variação Genética / Transtornos Cognitivos / Proteínas Vesiculares de Transporte de Monoamina / Lesões Encefálicas Traumáticas Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Variação Genética / Transtornos Cognitivos / Proteínas Vesiculares de Transporte de Monoamina / Lesões Encefálicas Traumáticas Idioma: En Ano de publicação: 2017 Tipo de documento: Article