Posttraumatic Brain Injury Cognitive Performance Is Moderated by Variation Within ANKK1 and DRD2 Genes.
Posttraumatic Brain Injury Cognitive Performance Is Moderated by Variation Within ANKK1 and DRD2 Genes.
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DOI：
10.1097/htr.0000000000000118
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
Wagner AK
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文献类型：
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作者：
Failla MD;Myrga JM;Ricker JH;Dixon CE;Conley YP;Wagner AK
随着多巴胺神经传递对认知的影响，我们假设连接的多巴胺D2受体(DRD2)和锚蛋白重复序列和激酶结构域(ANKK1)基因的变异可能解释了脑外伤后认知恢复的一些个体差异。108名重型颅脑损伤幸存者的前瞻性队列，从一级创伤中心连续招募。我们研究了脑外伤后6个月和12个月DRD2基因变异与功能恢复之间的关系。通过针对不同认知域的8项神经心理学测试来评估认知能力。本研究以标准化数据为基础，编制了一套完整的认知结构。我们还评估了功能性认知、抑郁状态和总体结果。受试者进行了6个DRD2标记单核苷酸多态和ANKK1内Taq1A的基因分型。在损伤后的两个时间点，ANKK1 Taq1A杂合子在几个认知域上的表现都好于纯合子。在调整了年龄、GCS和教育程度后，Taq1a(ANKK1)和rs6279(DRD2)变异与脑损伤后6个月的总体综合评分相关(p分别为0.0468和0.0430)。在12个月时，只有Taq1a仍然是认知的显著遗传预测因子(p=0.0128)。经过多重比较校正后，所检查的基因变异与功能性认知、抑郁状态和总体结果之间没有显著的关联。这些数据表明，DRD2内的基因变异影响脑损伤后的认知恢复。了解脑外伤后遗传对多巴胺能系统的影响可能会影响目前的治疗模式。
As dopamine neurotransmission impacts cognition, we hypothesized variants in the linked dopamine D2 receptor (DRD2) and ankyrin repeat and kinase domain (ANKK1) genes might account for some individual variability in cognitive recovery post-TBI. Prospective cohort of 108 survivors of severe TBI, recruited consecutively from a level 1 trauma center. We examined relationships between DRD2 genetic variation and functional recovery at 6 and 12 months post-TBI. Cognitive performance was evaluated using 8 neuropsychological tests targeting different cognitive domains. An overall cognitive composite was developed based on normative data. We also assessed functional cognition, depression status, and global outcome. Subjects were genotyped for 6 DRD2 tagging single nucleotide polymorphisms and Taq1A within ANKK1. ANKK1 Taq1A heterozygotes performed better than homozygotes across several cognitive domains at both time-points post-injury. When adjusting for age, GCS, and education, the Taq1A (ANKK1) and rs6279 (DRD2) variants were associated with overall composite scores at 6 months post-TBI (p=0.0468, 0.0430, respectively). At 12 months, only Taq1A remained a significant genetic predictor of cognition (p=0.0128). Following multiple comparisons correction, there were no significant associations between examined genetic variants and functional cognition, depression status, and global outcome. These data suggest genetic variation within DRD2 influences cognitive recovery post-TBI. Understanding genetic influences on dopaminergic systems post-TBI may impact current treatment paradigms.