Genetic Variation in the Vesicular Monoamine Transporter: Preliminary Associations With Cognitive Outcomes After Severe Traumatic Brain Injury.
Genetic Variation in the Vesicular Monoamine Transporter: Preliminary Associations With Cognitive Outcomes After Severe Traumatic Brain Injury.
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DOI：
10.1097/htr.0000000000000224
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Wagner AK
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文献类型：
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作者：
Markos SM;Failla MD;Ritter AC;Dixon CE;Conley YP;Ricker JH;Arenth PM;Juengst SB;Wagner AK
创伤性脑损伤 (TBI) 经常导致认知功能受损，而认知功能可以通过单胺能信号调节。单胺能基因之间的遗传变异可能会影响 TBI 后的认知表现。鉴于 VMAT2 在单胺能神经传递中的作用，囊泡单胺转运蛋白 2 (VMAT2) 基因可能是遗传变异的新来源，对 TBI 后的认知结果很重要。评估 VMAT2 变异性与 TBI 后认知结果之间的关联。我们使用标记单核苷酸多态性 (tSNP) 方法（rs363223、rs363226、rs363251 和 rs363341）评估了 136 名患有严重 TBI 的白人成年人的 VMAT2 变异。我们发现，遗传变异与评估的认知障碍 [认知综合 T 分数 (Comp-Cog)] 相互作用，从而影响损伤后 6 个月和 12 个月的功能认知 [功能独立测量认知分量表 (FIM-Cog)]。损伤后 6 个月的多变量分析显示 rs363226 基因型与 Comp-Cog 相关 (p=0.040)，并与 Comp-Cog 相互作用影响功能认知 (p<0.001)。 G纯合子的认知障碍最大，其认知障碍对功能认知的不利影响最大。我们提供了第一个证据，证明 VMAT2 内的遗传变异与 TBI 后的认知结果相关。需要进一步的工作来验证这一发现并阐明遗传变异影响单胺能信号传导、调节认知结果差异的机制。
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. Evaluate associations between VMAT2 variability and cognitive outcomes post-TBI. 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 T-scores (Comp-Cog)] to influence functional cognition [Functional Independence Measure Cognitive subscale (FIM-Cog)] 6 and 12 months post-injury. Multivariate analyses at 6-months post-injury showed rs363226 genotype was associated with Comp-Cog (p=0.040) and interacted with Comp-Cog to influence functional cognition (p<0.001). G-homozygotes had the largest cognitive impairment, and their cognitive impairment had the greatest adverse effect on functional cognition. We provide the first evidence that genetic variation within VMAT2 is associated with cognitive outcomes following TBI. Further work is needed to validate this finding and elucidate mechanisms by which genetic variation affects monoaminergic signaling, mediating differences in cognitive outcomes.